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Product listing: CBFβ (D4N2N) Rabbit mAb, UniProt ID Q13951 #62184 to MSH6 (3E1) Mouse mAb, UniProt ID P52701 #12988

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Chromatin IP, Western Blotting

Background: Core-binding factor subunit β (CBFβ) is a non-DNA binding transcription factor subunit that associates with and regulates the DNA binding activity of RUNX1, RUNX2, and RUNX3 (1). CBFβ is ubiquitously expressed and has been implicated in a variety of developmental processes including hematapoiesis, T cell development, chondrogenesis, and bone formation (2-7). In addition, investigators have identified CBFβ as one of the most frequently translocated genes in leukemia (8) and research studies have found it to be required for HIV immune evasion (9,10). CBFβ interacts with the viral protein VIF and triggers assembly of a ubiquitin ligase complex that targets the retroviral inhibitor APOBEC3G for degradation (9,10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: Valosin-containing protein (VCP) is a highly conserved and abundant 97 kDa protein that belongs to the AAA (ATPase associated with a variety of cellular activities) family of proteins. VCP assembles as a homo-hexamer, forming a ring with a channel at its center (1,2,3). VCP homo-hexamers associate with a variety of protein cofactors to form many distinct protein complexes, which act as chaperones to unfold proteins and transport them to specific cellular compartments or to the proteosome (4). These protein complexes participate in many cellular functions, including vesicle transport and fusion, fragmentation and reassembly of the golgi stacks during mitosis, nuclear envelope formation and spindle disassembly following mitosis, cell cycle regulation, DNA damage repair, apoptosis, B- and T-cell activation, NF-κB-mediated transcriptional regulation, endoplasmic reticulum (ER)-associated degradation and protein degradation (4). VCP appears to localize mainly to the endoplasmic reticulum; however, tyrosine phosphorylation is associated with relocalization to the centrosome during mitosis (5). In addition, following cellular exposure to ionizing radition, VCP is phosphorylated at Ser784 in an ATM-dependent manner and accumulates in the nucleus at sites of double-stranded DNA breaks (DSBs) (6). Exposure to other types of DNA damaging agents such as UV light, bleomycin or doxorubicin results in phosphorylation of VCP by ATR and DNA-PK in an ATM-independent manner (6).

$293
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry, Immunohistochemistry (Paraffin), Western Blotting

Background: Antigen receptors found on the surface of B cells contain a heterodimeric signaling component composed of CD79A and CD79B, also known as Ig α and Ig β, respectively (1,2). Presence of this receptor complex is essential for B-cell development and function (3). Together these two proteins and the associated B cell receptor initiate intracellular signaling following antigen binding (4,5). An immunoreceptor tyrosine-based activation motif (ITAM) found in the CD79A intracellular region appears to be important for its function (6). Antigen binding precedes formation of the CD79A and CD79B heterodimer and subsequent activation of receptor associated kinases (7). Research has shown that CD79A is a marker for B-lineage lymphoblastic leukemia (8). Additionally, investigators have found that mutations in the CD79A (MB1) gene are associated with abnormally low levels of functional B cell receptors in some cases of chronic B cell lymphocytic leukemia (9).

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse

Application Methods: Western Blotting

Background: CD14 is a leucine-rich repeat-containing pattern recognition receptor with expression largely restricted to the monocyte/macrophage cell lineage (1). Research studies have shown that CD14 is a bacterial lipopolysaccharide (LPS) binding glycoprotein, expressed as either a GPI-linked membrane protein or a soluble plasma protein (2). LPS induces an upregulation of GPI-linked CD14 expression, which facilitates TLR4 signaling and macrophage activation in response to bacterial infection (3-5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: hERG1(human ether-a-go-go-related gene potassium channel 1) is a voltage gated potassium channel alpha-subunit which mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr) (1,2). The hERG channel is composed of two subunits, 1a and 1b, which differ at amino terminus due to alternative splicing. Native hERG channels are heteromers of hERG1a with hERG1b. Both subunits contribute to IKr current (3-6).Blockade of hERG currents induced by compounds or mutation of hERG encoding gene-KCNH2 causes ventricular arrhythmias associated with inherited and acquired long QT syndrome and cardiomyocyte apoptosis (7-10). Therefore, hERG channel is a primary target for the development of class III antiarrhythmic agents (11,12). The hERG channel is also inhibited by a variety of non-antiarrhythmic compounds, which result in side effects. Consequently, hERG channel blockage is a common counter screen when selecting therapeutic agents for various diseases (11,13,14).Research studies have implicated hERG in cancer cell survival (15). In normal human adult tissue, hERG is expressed in heart, brain, myometrium, pancreas, and hematopoietic progenitors (16,17). hERG is expressed in various cancer cell lines of epithelial, neuronal, leukemic, and connective tissue origin but not in corresponding normal cells (18-22). Furthermore, hERG expression is associated with enhanced cancer cell proliferation, invasiveness, and poor prognosis (23,24).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Transient receptor potential (TRP) canonical 6 (TRPC6) belongs to the superfamily of TRP cation channels. The TRPC subfamily (TRPC1-7) is a group of calcium-permeable cation channels that mediates the increase in intracellular [Ca2+] following activation by G-protein-coupled receptors or receptor tyrosine kinases (1). TRPC6 is directly activated by diacylglycerol (DAG) (2). Various tissues express TRPC6, including brain, lung, kidney, ovary and small intestine. TRPC6 exerts a variety of biological functions in various tissues. In brain, TRPC6 plays important roles in synaptic plasticity, spatial cognition (3) and protects neurons from ischemic excitotoxicity (4). In kidney, TRPC6 is expressed in mesangial cells and podocytes of renal glomeruli (5) and regulates glomerular filtration (6). Mutations in TRPC6 gene cause autosomal dominant focal segmental glomerulosclerosis (7). In smooth muscle cells, TRPC6 mediates Na+ influx followed by Ca2+ entry via Na+/Ca2+ -exchanger (NCX) reversal which leads to contraction (8, 9).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: Histone macroH2A1 and macroH2A2 comprise a family of variant histone H2A proteins. MacroH2A1 exists as two distinct isoforms due to alternative splicing of a single gene; macroH2A1.1 levels accumulate throughout differentiation and development while macroH2A1.2 shows a constant level of expression (1). MacroH2A1 and macroH2A2 are encoded by completely distinct genes located on separate chromosomes (2,3). Both macroH2A1 and macroH2A2 proteins contain an amino-terminal histone-like region with 64% sequence identity to canonical histone H2A, in addition to a carboxy-terminal “macro” domain (1-3). MacroH2A1 and macroH2A2 are enriched in facultative heterochromatin, including inactivated X chromosomes in mammalian females and senescence-associated heterochromatin foci (2-5). Both act to repress gene transcription by inhibiting the binding of transcription factors to chromatin, the acetylation of histones by p300, and the chromatin-remodeling activities of SWI/SNF and ACF (6,7). The macro domain of macroH2A1.1 binds to ADP-ribose and functions to recruit macroH2A1.1 to activated PARP at sites of DNA damage, where it mediates chromatin rearrangements to locally regulate the DNA damage response (8). MacroH2A1.2 and macroH2A2 do not bind poly-ADP-ribose and are not recruited to sites of activated PARP (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse

Application Methods: Chromatin IP, Chromatin IP-seq, Western Blotting

Background: Methylation of DNA at cytosine residues is a heritable, epigenetic modification that is critical for proper regulation of gene expression, genomic imprinting, and mammalian development (1,2). 5-methylcytosine is a repressive epigenetic mark established de novo by two enzymes, DNMT3a and DNMT3b, and is maintained by DNMT1 (3, 4). 5-methylcytosine was originally thought to be passively depleted during DNA replication. However, subsequent studies have shown that Ten-Eleven Translocation (TET) proteins TET1, TET2, and TET3 can catalyze the oxidation of methylated cytosine to 5-hydroxymethylcytosine (5-hmC) (5). Additionally, TET proteins can further oxidize 5-hmC to form 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), both of which are excised by thymine-DNA glycosylase (TDG), effectively linking cytosine oxidation to the base excision repair pathway and supporting active cytosine demethylation (6,7). TET2 is the most frequently mutated gene in myeloid dysplastic syndrome (MDS), a dysplasia of myeloid, megakaryocytic, and/or erythroid cell lineages, of which 30% progress to acute myeloid leukemia (AML) (8, 9). It is also mutated in diffuse large B-cell lymphoma (10). TET2 protein expression is often reduced in solid tumors such as prostate cancer, melanoma, and oral squamous cell carcinoma (11-13).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: Rab6 is a member of the Ras superfamily of small Rab GTPases implicated in endocytosis (1). The three distinct members of the Rab6 subfamily (Rab6A, Rab6A', and Rab6B) are structurally similar but likely exhibit non-overlapping functions (2,3). Rab6 localized to the Golgi (4) regulates retrograde transport of membrane-bound target proteins from the Golgi apparatus to the endoplasmic reticulum (5-7) or from the Golgi to the endosome during exocytotic transport (8). Rab6 interacts with microtubule motor proteins such as rabkinesin-6 (KIF20A) and dynein/dynactin complexes; Rab6-mediated transport requires a functionally intact microtubule system (9,10). Rab6 also regulates cytokinesis and cell cycle check point through interactions with Rab6 effector proteins, including the dynein/dynactin protein DCTN1 and the GTPase activating protein RABGAP1 (11,12).

$122
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Western Blotting

Background: The Grb-associated binder (Gab) family is a family of adaptor proteins recruited by a wide variety of receptor tyrosine kinases (RTKs) such as EGFR, HGFR, insulin receptor, cytokine receptor and B cell antigen receptors. Upon stimulation of RTKs by their cognate ligand, Gab is recruited to the plasma membrane where it is phosphorylated and functions as a scaffold (1-4). Multiple tyrosine phosphorylation sites of Gab1 protein have been identified (5). Phosphorylation of Tyr472 regulates its binding to p85 PI3 kinase (6,7). Phosphorylation of Gab1 at Tyr307, Tyr373 and Tyr407 modulates its association to PLCγ (8). Phosphorylation of Tyr627 and Tyr659 is required for Gab1 binding to and activation of the protein tyrosine phosphatase SHP2 (6,9).

$122
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Flow Cytometry, Immunohistochemistry (Paraffin), Western Blotting

Background: Heat shock protein (HSP) 27 is one of the small HSPs that are constitutively expressed at different levels in various cell types and tissues. Like other small HSPs, HSP27 is regulated at both the transcriptional and posttranslational levels (1). In response to stress, the HSP27 expression increases several-fold to confer cellular resistance to the adverse environmental change. HSP27 is phosphorylated at Ser15, Ser78, and Ser82 by MAPKAPK-2 as a result of the activation of the p38 MAP kinase pathway (2,3). Phosphorylation of HSP27 causes a change in its tertiary structure, which shifts from large homotypic multimers to dimers and monomers (4). It has been shown that phosphorylation and increased concentration of HSP27 modulates actin polymerization and reorganization (5,6).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Chromatin IP, Chromatin IP-seq, Immunofluorescence (Immunocytochemistry), Western Blotting

Background: NKX3.1 is a homeobox transcription factor that in mammals plays a defining role in embryonic prostate morphogenesis. The expression of mammalian NKX3.1 is androgen-dependent, restricted primarily to developing and mature prostate epithelium, and is frequently reduced or lost in prostate cancer (1-3). The human NKX3.1 gene is located on chromsome 8p21.2, within a region that shows loss of heterozygosity (LOH) in >50% of prostate cancer cases (2). Allelic loss at the NKX3.1 locus is also common in high grade Prostate Intraepithelial Neoplasia (PIN), thought to be a putative precursor lesion to invasive prostate adenocarcinomas, suggesting that LOH at the NKX3.1 locus is a critical early step in prostate cancer development (4). Notably, the remaining NKX3.1 allele is intact in the majority of LOH cases, leading to the suggestion that NKX3.1 functions as a haploinsufficient tumor suppressor (4-6). Due to its highly restricted expression in prostate epithelial cells, NKX3.1 has been suggested as a diagnostic marker of prostate carcinoma (7), and may have additional utility as a biomarker of metastatic lesions originating in the prostate (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Integrins are α/β heterodimeric cell surface receptors that play a pivotal role in cell adhesion and migration, as well as in growth and survival (1,2). The integrin family contains at least 18 α and 8 β subunits that form 24 known integrins with distinct tissue distribution and overlapping ligand specificities (3). Integrins not only transmit signals to cells in response to the extracellular environment (outside-in signaling), but also sense intracellular cues to alter their interaction with extracellular environment (inside-out signaling) (1,2).Integrin β4 pairs with integrin α6 on the cell surface membrane to form the integrin α6β4 heterodimer, an important laminin receptor that is essential for hemidesmosome formation and the support of stable adhesions between basal epithelial cells and the basement membrane (4,5). Integrin β4 is an important component in several growth factor induced signaling pathways that are involved in tumorigenesis and invasive cell growth (6,7).

$305
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct flow cytometric analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated Mcl-1 (D2W9E) Rabbit mAb #94296.
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Flow Cytometry

Background: Mcl-1 is an anti-apoptotic member of the Bcl-2 family originally isolated from the ML-1 human myeloid leukemia cell line during phorbol ester-induced differentiation along the monocyte/macrophage pathway (1). Similar to other Bcl-2 family members, Mcl-1 localizes to the mitochondria (2), interacts with and antagonizes pro-apoptotic Bcl-2 family members (3), and inhibits apoptosis induced by a number of cytotoxic stimuli (4). Mcl-1 differs from its other family members in its regulation at both the transcriptional and post-translational level. First, Mcl-1 has an extended amino-terminal PEST region, which is responsible for its relatively short half-life (1,2). Second, unlike other family members, Mcl-1 is rapidly transcribed via a PI3K/Akt dependent pathway, resulting in its increased expression during myeloid differentiation and cytokine stimulation (1,5-7). Mcl-1 is phosphorylated in response to treatment with phorbol ester, microtubule-damaging agents, oxidative stress, and cytokine withdrawal (8-11). Phosphorylation at Thr163, the conserved MAP kinase/ERK site located within the PEST region, slows Mcl-1 protein turnover (10) but may prime the GSK-3 mediated phosphorylation at Ser159 that leads to Mcl-1 destabilization (11). Mcl-1 deficiency in mice results in peri-implantation lethality (12). In addition, conditional disruption of the corresponding mcl-1 gene shows that Mcl-1 plays an important role in early lymphoid development and in the maintenance of mature lymphocytes (13).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: The NFAT (nuclear factor of activated T cells) family of proteins consists of NFAT1 (NFATc2 or NFATp), NFAT2 (NFATc1 or NFATc), NFAT3 (NFATc4), and NFAT4 (NFATc3 or NFATx). All members of this family are transcription factors with a Rel homology domain and regulate gene transcription in concert with AP-1 (Jun/Fos) to orchestrate an effective immune response (1,2). NFAT proteins are predominantly expressed in cells of the immune system, but are also expressed in skeletal muscle, keratinocytes, and adipocytes, regulating cell differentiation programs in these cells (3). In resting cells, NFAT proteins are heavily phosphorylated and localized in the cytoplasm. Increased intracellular calcium concentrations activate the calcium/calmodulin-dependent serine phosphatase calcineurin, which dephosphorylates NFAT proteins, resulting in their subsequent translocation to the nucleus (2). Termination of NFAT signaling occurs upon declining calcium concentrations and phosphorylation of NFAT by kinases such as GSK-3 or CK1 (3,4). Cyclosporin A and FK506 are immunosuppressive drugs that inhibit calcineurin and thus retain NFAT proteins in the cytoplasm (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: PHD finger protein 19 (PHF19), also known as polycomb-like protein 3 (PCL3), is a polycomb group protein that functions as an accessory subunit of the polycomb repressor complex 2 (PRC2), which represses target gene expression through methylation of histone H3 at lysine 27 by the EZH2 methyltransferase (1). PHF19 recruits PRC2 to target genes by binding trimethylated histone H3 lysine 36, a mark of active chromatin, via its Tudor domain (2-4). PHF19 associates with PRC2 and the histone H3 lysine 36 demethylases NO66 and FBXL10, and is required to recruit PRC2 and NO66/FBXL10 to stem cell genes during differentiation, resulting in PRC2-mediated trimethylation of histone H3 lysine 27, loss of trimethylated histone H3 lysine 36, and transcriptional silencing (2-4). Thus, PHF19 is critical for the proper transition of stem cell genes from the active to inactive state during differentiation of embryonic stem cells.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Chromatin IP, Western Blotting

Background: POLR3A is the largest subunit of the DNA-dependent RNA polymerase III, one of the DNA-dependent RNA polymerases that transcribe small non-coding RNAs such as the 5S rRNA, tRNAs and some miRNAs (1-3). Together with the second largest subunit, POLR3A forms the catalytic center of the polymerase (4). In addition, RNA polymerase III plays a role in the innate immune response by sensing non-self double stranded DNA. Transcription of the non-self DNA into RNA induces type I interferon production through the RIG-I pathway (5,6). Studies suggest that mutations in the POLR3A gene may be linked to hypomyelinating leukodystrophies; a group of inherited neurodegenerative disorders (7-9).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: The process of SUMO-1 conjugation is similar to that seen with ubiquitin and other forms of post-translational protein modification (1). Like ubiquitin, SUMO-1 is conjugated to its target protein by the coordinated action of ubiquitin conjugation enzymes E1, E2 and E3 (2). Ubc9 (or ube2M) is a highly conserved, 158 amino acid protein that acts as a SUMO-1 conjugating enzyme (3). Ubc9 binds to target proteins through their SUMO-1-CS (consensus sequence) domains and interacts with SUMO via the structurally conserved amino-terminal domain (3,4). Localization of Ubc9 to the nucleus and the nuclear envelope allows this enzyme to catalyze target protein sumoylation and regulate target protein nucleocytoplasmic transport and transcriptional activity (5,6). Ubc9 target proteins include a host of proteins (RAD51, RAD52, p53 and c-Jun) that regulate the cell cycle, DNA repair, and p53-dependent processes (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Vascular endothelial growth factor (VEGF) is a highly specific mitogen for vascular endothelial cells. VEGF and its close relatives VEGF-B, -C and -D form a subfamily within PDGF family of growth factors, which belongs to the cysteine knot class of cytokines. Five VEGF isoforms of 121, 145, 165, 189 and 206 amino acids (VEGF121–206) are generated as a result of alternative splicing from a single VEGF gene (1).The various VEGF forms bind to three tyrosine-kinase receptors, VEGFR-1, VEGFR-2 and VEGFR-3 which are expressed almost exclusively in endothelial cells. VEGFR-2 is the main angiogenic signal transducer for VEGF, while VEGFR-3 is specific for VEGF-C and -D and is necessary and sufficient for lymphangiogenic signaling. However, upon proteolytic processing VEGF-C and -D gain the ability to also bind and activate VEGFR-2 (2). Guided by the binding properties of the ligands, the VEGFRs are able to form both homodimers and heterodimers. Receptor dimerization is accompanied by activation of receptor kinase activity leading to receptor autophosphorylation. Phosphorylated receptors recruit interacting proteins and induce downstream signaling (3). Recently, tumor therapies based on neutralizing anti-VEGF antibodies and small molecule tyrosine kinase inhibitors targeting VEGFRs have been developed. These new strategies for tumor treatment show the clinical relevance of inhibiting VEGF signal transduction pathways that are exaggerated in pathological angiogenesis (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry), Western Blotting

Background: Aurora A (AIK) is a cell cycle-regulated Ser/Thr protein kinase that is overexpressed in many tumor cell lines (1-3). Phosphorylation of Aurora A at Thr288 within the kinase activation loop results in a significant increase in its activity and may target the protein for proteasomal degradation during mitosis (4). The closely-related kinase Aurora B (AIM1) has been implicated in multiple mitotic events (5), and siRNA silencing of Aurora B expression results in reduced histone H3 phosphorylation, aberrant chromosome alignment/segregation, and altered survivin localization (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Human progesterone receptor (PR) is expressed as two forms: the full length PR-B and the short form PR-A. PR-A lacks the first 164 amino acid residues of PR-B (1,2). Both PR-A and PR-B are ligand activated, but differ in their relative ability to activate target gene transcription (3,4). The activity of PR is regulated by phosphorylation; at least seven serine residues are phosphorylated in its amino-terminal domain. Three sites (Ser81, Ser102, and Ser162) are unique to full length PR-B, while other sites (Ser190, Ser294, Ser345, and Ser400) are shared by both isoforms (5). Phosphorylation of PR-B at Ser190 (equivalent to Ser26 of PR-A) is catalyzed by CDK2 (6). Mutation of Ser190 results in decreased activity of PR (7), suggesting that the phosphorylation at Ser190 may be critical to its biological function.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: The mediator complex consists of about 25-30 proteins and is thought to facilitate transcription activation by acting as a molecular bridge between the RNA polymerase II (RNAPII) machinery and transcription factors (1). Mediator is recruited to target genes by transcription factors and plays an essential role in the recruitment and stabilization of the RNAPII transcription complex at promoters, as well as the activation of transcription post RNAPII recruitment (1-5). The mediator complex also plays an important role in creating ‘chromatin loops’ that occur as a result of interactions between the transcription factor bound at distal enhancers and RNAPII bound at the proximal promoter, and works to sustain proper chromatin architecture during active transcription (6-8).

$262
50-100 transfections
300 µl
SignalSilence® p53 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit p53 expression using RNA interference, a method whereby gene expression can be selectively silenced through the delivery of double stranded RNA molecules into the cell. All SignalSilence® siRNA products from CST are rigorously tested in-house and have been shown to reduce target protein expression by western analysis.
REACTIVITY
Human

Background: The p53 tumor suppressor protein plays a major role in cellular response to DNA damage and other genomic aberrations. Activation of p53 can lead to either cell cycle arrest and DNA repair or apoptosis (1). p53 is phosphorylated at multiple sites in vivo and by several different protein kinases in vitro (2,3). DNA damage induces phosphorylation of p53 at Ser15 and Ser20 and leads to a reduced interaction between p53 and its negative regulator, the oncoprotein MDM2 (4). MDM2 inhibits p53 accumulation by targeting it for ubiquitination and proteasomal degradation (5,6). p53 can be phosphorylated by ATM, ATR, and DNA-PK at Ser15 and Ser37. Phosphorylation impairs the ability of MDM2 to bind p53, promoting both the accumulation and activation of p53 in response to DNA damage (4,7). Chk2 and Chk1 can phosphorylate p53 at Ser20, enhancing its tetramerization, stability, and activity (8,9). p53 is phosphorylated at Ser392 in vivo (10,11) and by CAK in vitro (11). Phosphorylation of p53 at Ser392 is increased in human tumors (12) and has been reported to influence the growth suppressor function, DNA binding, and transcriptional activation of p53 (10,13,14). p53 is phosphorylated at Ser6 and Ser9 by CK1δ and CK1ε both in vitro and in vivo (13,15). Phosphorylation of p53 at Ser46 regulates the ability of p53 to induce apoptosis (16). Acetylation of p53 is mediated by p300 and CBP acetyltransferases. Inhibition of deacetylation suppressing MDM2 from recruiting HDAC1 complex by p19 (ARF) stabilizes p53. Acetylation appears to play a positive role in the accumulation of p53 protein in stress response (17). Following DNA damage, human p53 becomes acetylated at Lys382 (Lys379 in mouse) in vivo to enhance p53-DNA binding (18). Deacetylation of p53 occurs through interaction with the SIRT1 protein, a deacetylase that may be involved in cellular aging and the DNA damage response (19).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Cell proliferation in all eukaryotic cells depends strictly upon the ubiquitin ligase (E3) activity of the anaphase promoting complex/cyclosome (APC/C), whose main function is to trigger the transition of the cell cycle from metaphase to anaphase. APC/C performs its various functions by promoting the assembly of polyubiquitin chains on substrate proteins, which targets these proteins for degradation by the 26S proteasome (1,2). In humans, twelve different APC/C subunits have been identified. Like all E3 enzymes, APC/C utilizes ubiquitin residues that have been activated by E1 enzymes and then transferred to E2 enzymes. Indeed, APC/C has been shown to interact with UBE2S and UBE2C E2 enzymes, in part, via the RING-finger domain-containing subunit, APC11 (3-5). APC/C activity is also strictly dependent upon its association with multiple cofactors. For example, the related proteins, Cdc20 and Cdh1/FZR1, participate in the recognition of APC/C substrates by interacting with specific recognition elements in these substrates (6), called D-boxes (7) and KEN-boxes (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: BLM, a member of the RecQ family of DNA helicases, is part of the BRCA1-associated genome surveillance complex (BASC) that responds to DNA damage, stalled replication forks and S phase arrest (1-4). Phosphorylation of BLM helicase at Thr99 and Thr122 occurs in response to genotoxic stress (4), and phosphorylation of Ser144 appears to be important in regulating chromosome stability during mitosis (5). Typical BLM protein resides in the nucleus and forms part of a dynamic protein complex that acts in response to DNA damage during specific periods of the cell cycle (6). Although RecQ helicases are rarely considered as essential enzymes, they function at the interface between DNA recombination and repair and are required for global genome stability maintenance. Mutations in BLM helicase are responsible for development of Bloom Syndrome, a recessive genetic disorder clinically characterized by short stature, immunodeficiency and elevated risk of malignancy (7). Similar alterations to genes encoding the related RecQ helicases RecQ4 and WRN also result in recessive genetic disorders associated with genomic instability (8,9). Cells from Bloom Syndrome patients exhibit genomic instability and increased frequency of sister chromatid exchange (10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: There are two isoforms of Sec23 protein: Sec23A and Sec23B. Both isoforms have been shown in the Sec23/24 complex, which is a component of COPII coat (1). COPII is composed of at least five proteins: the Sec23/24 complex, the Sec13/31 complex, and Sar1. COPII coat is located at the ER/Golgi interface and involved in transport of newly synthesized proteins from the ER to the Golgi apparatus (2). COPII formation is initiated through binding of the activated G protein, Sar1, to the Sec23/24 complex to form a prebudding complex, which directly binds target molecules (2-4). The prebudding complex further recruits Sec13/31 to form mature COPII coat (5,6). In addition to being a COPII component, Sec23 has also been shown to interact with p125 and Sec16 at the transitional ER; these interactions are important for regulation of the COPII transportation function (7,8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Despite their relatively small size (8-12 kDa) and uncomplicated architecture, S100 proteins regulate a variety of cellular processes such as cell growth and motility, cell cycle progression, transcription, and differentiation. To date, 25 members have been identified, including S100A1-S100A18, trichohyalin, filaggrin, repetin, S100P, and S100Z, making it the largest group in the EF-hand, calcium-binding protein family. Interestingly, 14 S100 genes are clustered on human chromosome 1q21, a region of genomic instability. Research studies have demonstrated that significant correlation exists between aberrant S100 protein expression and cancer progression. S100 proteins primarily mediate immune responses in various tissue types but are also involved in neuronal development (1-4).Each S100 monomer bears two EF-hand motifs and can bind up to two molecules of calcium (or other divalent cation in some instances). Structural evidence shows that S100 proteins form antiparallel homo- or heterodimers that coordinate binding partner proximity in a calcium-dependent (and sometimes calcium-independent) manner. Although structurally and functionally similar, individual members show restricted tissue distribution, are localized in specific cellular compartments, and display unique protein binding partners, which suggests that each plays a specific role in various signaling pathways. In addition to an intracellular role, some S100 proteins have been shown to act as receptors for extracellular ligands or are secreted and exhibit cytokine-like activities (1-4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: The retinoblastoma (Rb) tumor suppressor family includes the retinoblastoma protein Rb (p105), retinoblastoma-like protein 1 (RBL1, p107), and retinoblastoma-like protein 2 (RBL2, p130). These Rb family proteins are referred to as "pocket proteins" because they contain a conserved binding pocket region that interacts with critical regulatory proteins, including E2F family transcription factors, c-Abl tyrosine kinase, and proteins containing a conserved LXCXE motif (1,2). In quiescent G0 phase cells, active Rb proteins hypophosphorylate and bind to E2F transcription factors to repress transcription and inhibit cell cycle progression (1,2). Upon growth factor induction of quiescent cells, Rb proteins become hyperphosphorylated and inactivated by G1-phase cyclinD-cdk4/6, G1/S-phase cyclin E-cdk2, and G1/S-phase cyclin A-cdk2 complexes (1,2). Hyperphosphorylation of Rb proteins results in a loss of E2F binding and allows for transcriptional activation and cell cycle progression (1,2). In addition to regulating the cell cycle, Rb proteins regulate chromosome stability, induction, and maintenance of senescence, apoptosis, cellular differentiation, and angiogenesis (3).Retinoblastoma-like protein 1 (RBL1, p107) interacts with E2F4 and E2F5 to recruit the DP, RB-like, E2F, and MuvB protein (DREAM) complex to E2F target genes to repress transcription of multiple genes required for progression into S phase and mitosis (4-6). Hypophosphorylation of RBL1 during cellular senescence is required for maintenance of senescent cells (7,8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Dickkopf (DKK) family proteins consist of four members DKK1, DKK2, DKK3 and DKK4 that function as secreted Wnt antagonists by inhibiting Wnt coreceptors LRP5 and LRP6 (1,2). DKKs contain two cysteine-rich domains in which the positions of 10 cysteine residues are well conserved (3). Their expression is both temporally and spatially regulated during animal development (4). DKKs also bind with high affinity to transmembrane proteins Kremen1 and 2, which themselves also modulate Wnt signaling (5,6).

$269
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Western Blotting

Background: The DNA mismatch repair system (MMR) repairs post-replication DNA, inhibits recombination between nonidentical DNA sequences, and induces both checkpoint and apoptotic responses following certain types of DNA damage (1). MSH2 (MutS homologue 2) forms the hMutS-α dimer with MSH6 and is an essential component of the mismatch repair process. hMutS-α is part of the BRCA1-associated surveillance complex (BASC), a complex that also contains BRCA1, MLH1, ATM, BLM, PMS2 proteins, and the Rad50-Mre11-NBS1 complex (2). Mutations in MSH6 and other MMR proteins have been found in a large proportion of hereditary nonpolyposis colorectal cancer (Lynch Syndrome), the most common form of inherited colorectal cancer in the Western world (3). Mutations in MSH6 have been shown to occur in glioblastoma in response to temozolomide therapy and to promote temozolomide resistance (4).