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Product listing: UVRAG (D2Q1Z) Rabbit mAb, UniProt ID Q9P2Y5 #13115 to SignalSilence® SET8 siRNA I, UniProt ID Q9NQR1 #13067

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: Autophagy is a catabolic process for the autophagosomic-lysosomal degradation of bulk cytoplasmic contents (1,2). It is generally activated by conditions of nutrient deprivation but has also been associated with a number of physiological processes including development, differentiation, neurodegeneration, infection and cancer (3). The molecular machinery of autophagy was largely discovered in yeast and referred to as autophagy-related (Atg) genes. These proteins are involved in the formation of cytoplasmic vacuoles called autophagosomes that are delivered to lysosomes for degradation.The class III type phosphoinositide 3-kinase (PI3KC3)/Vps34 regulates vacuolar trafficking as well as autophagy (4,5). Multiple proteins have been shown to be associated with Vsp34, including: p105/Vsp15, Beclin-1, UVRAG, Atg14, and Rubicon, which can determine Vsp34 function (6-11). UVRAG (UV radiation resistance-associated gene) is associated with the Beclin-1/PI3KC3 complex and promotes PI3KC3 enzymatic activity and autophagy, while suppressing proliferation (11). Beclin-1 binding to UVRAG promotes both autophagosome maturation and endocytic trafficking (12). UVRAG is also a potential tumor suppressor protein with frameshift mutations observed in colon and gastric carcinomas (13,14).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human

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

Background: Transferrin receptor 1 (CD71, TFRC) is a type II transmembrane receptor and carrier protein responsible for the uptake of cellular iron through receptor-mediated endocytosis (1). Neutral pH at the cell surface promotes binding of the iron-binding glycoprotein transferrin (Tf) to the CD71 receptor. The receptor-ligand complex enters the cell through receptor-mediated endocytosis and is internalized into an endosome. Relatively lower endosomal pH leads to a change in the local charge environment surrounding the iron-transferrin binding site and results in the release of iron (2). The receptor-ligand complex is recycled to the cell surface where transferrin dissociates from the CD71 receptor (2). Ubiquitously expressed transferrin receptor is continuously recycled and undergoes clathrin-mediated endocytosis regardless of ligand binding state. The interaction between receptor and ligand has been studied in detail. The helical domain of CD71 directly interacts with the transferrin C-lobe and induces a conformation change in Tf to facilitate the transport process (3). Interaction between the receptor CD71 and transferrin is mediated by the membrane protein hemochromatosis (HFE). HFE binds the α-helical domain of CD71, blocking formation of the CD71-transferrin complex and inhibiting iron uptake (4,5). In addition to binding transferrin, CD71 also interacts with H-ferritin at the cell surface and transports this intracellular iron storage protein to cellular endosomes and lysosomes (6). Additional studies indicate that the transferrin receptor is an evolutionarily conserved receptor for a number or arenaviruses and at least one retrovirus (7,8). Aberrant expression of CD71 is seen in a number of cancers, including thyroid carcinomas, lymphomas, and T-lineage leukemias, suggesting a possible therapeutic role for targeted inhibition of the transferrin receptor (9,10).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: CUB domain containing protein 1 (CDCP1, SIMA135) is a putative stem cell marker shown in research studies to be highly expressed in some human cancer cells and in both typical and atypical (cancerous) colons (1). Expression of CDCP1 may be epigenetically regulated, as methylation of promoter CpG sequences results in decreased CDCP1 expression (2). The corresponding CDCP1 gene encodes a glycoprotein that acts as a complex, multidomain transmembrane antigen. CDCP1 has three extracellular CUB domains that may be involved in cell adhesion or extracellular matrix interactions (1,3). Src-family kinases may phosphorylate CDCP1 at five tyrosine residues within its cytoplasmic domain to provide a potential binding site for SH2 domain-containing proteins (3). CDCP1 is a putative hematopoietic stem cell marker (4,5).

$129
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Flow Cytometry, Immunofluorescence (Frozen), Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: Proliferating cell nuclear antigen (PCNA) is a member of the DNA sliding clamp family of proteins that assist in DNA replication (1). Crystal structure data suggests that a PCNA homotrimer ring can encircle and slide along the DNA double helix (2). Multiple proteins involved in DNA replication, DNA repair, and cell cycle control bind to PCNA rather than directly associating with DNA, thus facilitating fast processing of DNA (reviewed in 3). PCNA protein expression is a well-accepted marker of proliferation.

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human

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

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). In addition to p53, mammalian cells contain two p53 family members, p63 and p73, which are similar to p53 in both structure and function (2). While p63 can induce p53-responsive genes and apoptosis, mutation of p63 rarely results in tumors (2). Research investigators frequently observe amplification of the p63 gene in squamous cell carcinomas of the lung, head and neck (2,3). The p63 gene contains an alternative transcription initiation site that yields a truncated ΔNp63 lacking the transactivation domain, and alternative splicing at the carboxy-terminus yields the α, β, and γ isoforms (3,4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

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

Background: Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the synthesis of the neurotransmitter dopamine and other catecholamines. TH functions as a tetramer, with each subunit composed of a regulatory and catalytic domain, and exists in several different isoforms (1,2). This enzyme is required for embryonic development since TH knockout mice die before or at birth (3). Levels of transcription, translation and posttranslational modification regulate TH activity. The amino-terminal regulatory domain contains three serine residues: Ser9, Ser31 and Ser40. Phosphorylation at Ser40 by PKA positively regulates the catalytic activity of TH (4-6). Phosphorylation at Ser31 by CDK5 also increases the catalytic activity of TH through stabilization of TH protein levels (7-9).

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

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

Background: The Set1 histone methyltransferase protein was first identified in yeast as part of the Set1/COMPASS histone methyltransferase complex, which methylates histone H3 at Lys4 and functions as a transcriptional co-activator (1). While yeast contain only one known Set1 protein, six Set1-related proteins exist in mammals: SET1A, SET1B, MLL1, MLL2, MLL3, and MLL4, all of which assemble into COMPASS-like complexes and methylate histone H3 at Lys4 (2,3). These Set1-related proteins are each found in distinct protein complexes, all of which share the common subunits WDR5, RBBP5, ASH2L, CXXC1 and DPY30. These subunits are required for proper complex assembly and modulation of histone methyltransferase activity (2-6). MLL1 and MLL2 complexes contain the additional protein subunit, menin (6). Like yeast Set1, all six Set1-related mammalian proteins methylate histone H3 at Lys4 (2-6). MLL translocations are found in a large number of hematological malignancies, suggesting that Set1/COMPASS histone methyltransferase complexes play a critical role in leukemogenesis (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Rat

Application Methods: Western Blotting

Background: SREBP cleavage activating protein (SCAP) is a membrane-bound protein essential in regulating sterol regulatory element binding protein (SREBP) processing (1). In cholesterol-starved cells, SREBPs move from the ER to the Golgi apparatus with the help of SCAP, where the precursor SREBPs are cleaved by site-1 (S1P) and site-2 (S2P) proteases (1,2). Released SREBP amino-terminal domains enter the nucleus and bind to sterol response elements located in the promoters of a number of genes responsible for the cholesterol synthesis (1,2). Research studies show that the SCAP/SREBP pathway is critical for diabetic fatty liver development and carbohydrate-induced hypertriglyceridemia in mice (3). In addition, the SCAP/SREBP pathway is required to protect cancer cells from lipotoxicity (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Ras-related protein Rab1A (Rab1A) is a member of the Ras superfamily of cellular G proteins that function in protein transport and membrane restructuring (1). Early immunofluorescence studies determined that Rab1A localizes to a region between the endoplasmic reticulum (ER) and the Golgi complex, and in early Golgi compartments (2). Rab1A binds and recruits the COPII complex tethering factor p115 to a cis-SNARE complex associated with COPII-coated, budding vesicles on the endoplasmic reticulum (3). A Rab1 effector complex containing several proteins, including the cis-Golgi tethering protein GM130 and the stacking protein GRASP65, is essential for targeting and fusion of COPII-coated vesicles with the Golgi complex (4). Rab1A also interacts with the golgin tethering and docking proteins giantin (GOLGB1) and golgin-84 to regulate Golgi structure formation and function (5,6). Thus, Rab1A plays an important role in mediating the export of newly synthesized target proteins from ER to the Golgi. As with other Rab proteins, Rab1A function requires an intrinsic GTPase cycling activity facilitated by associated GEF and GAP factors (7-9). In addition to mediating ER to Golgi transport, Rab1A is also involved in autophagy during early autophagosome formation (10,11).

$269
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunohistochemistry (Paraffin), Western Blotting

Background: Keratins (cytokeratins) are intermediate filament proteins that are mainly expressed in epithelial cells. Keratin heterodimers composed of an acidic keratin (or type I keratin, keratins 9 to 23) and a basic keratin (or type II keratin, keratins 1 to 8) assemble to form filaments (1,2). Keratin isoforms demonstrate tissue- and differentiation-specific profiles that make them useful as research biomarkers (1). Research studies have shown that mutations in keratin genes are associated with skin disorders, liver and pancreatic diseases, and inflammatory intestinal diseases (3-6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: PEA-15 is a 15 kDa phosphoprotein expressed abundantly in astrocytes and fibroblasts as well as in tissues, including the lung and eye (1). The protein has been shown to coordinate cell growth, death, and glucose utilization (2-4). The amino-terminal DED domain of PEA-15 mediates its binding to FADD or Erk and further regulates the Erk and apoptosis signaling pathways. PEA-15 can be phosphorylated at two serine residues, Ser104 and Ser116, located within the carboxy terminus. Phosphorylation at these sites regulates binding to Erk and FADD (2,3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

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

Background: Runt-related transcription factor 3 (RUNX3, AML2), a member of the Runt family of transcription factors, plays an important role in the suppression of gastric epithelium cell proliferation (1), dorsal root ganglia neurogenesis (2), and T cell differentiation (3,4). RUNX3 is also involved in caspase-3-dependent apoptosis (5). Protein complexes containing RUNX3 and various transcription factors, such as Smads or β-catenin/TCF4, have tumor suppressor activity and regulate downstream target gene transcription (6,7). While typically localized to the nucleus, RUNX3 can be tyrosine phosphorylated and located in the cytoplasm of many cancer cells. This mislocalization of RUNX3 abolishes its tumor suppressor function and contributes to tumorigenesis (8). Research studies indicate that gene silencing or protein mislocalization inactivates RUNX3 in more than 80% of gastric cancers and other cancer types (1,9,10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

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

Background: Eukaryotic initiation factor 4B (eIF4B) is thought to assist the eIF4F complex in translation initiation. In plants, eIF4B is known to interact with the poly-(A) binding protein, increasing its poly-(A) binding activity (1). Heat shock and serum starvation cause dephosphorylation of eIF4B at multiple sites with kinetics similar to those of the corresponding inhibition of translation, while phosphorylation of eIF4B following insulin treatment correlates well with an observed increase in translation (2-5). Multiple kinases, including p70 S6 kinase, can phosphorylate eIF4B in vitro, and at least one serum-inducible eIF4B phosphorylation site is sensitive to rapamycin and LY294002 (6). Recently, Ser406 was identified as a novel phosphorylation site regulated by mitogens (7), and the phosphorylation of this site is dependent on MEK and mTOR activity (7). This phosphorylation is shown to be essential for the translational activity of eIF4B (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: The high affinity copper uptake protein 1 (CTR1, SLC31A1) helps maintain copper homeostasis by mediating dietary copper intake chiefly in the small intestine (1). A series of methionine-rich repeats and other residues are conserved among CTR1 genes across taxa, and are thought to be important for copper transport (2,3). In mammalian cells, CTR1 is localized to the plasma membrane and intracellular vesicles (3). Upon copper uptake via plasma membrane into cells, CTR1 is down regulated by clathrin-dependent endocytosis and degradation of CTR1 protein (4). Research studies suggest that the CTR1 copper transporter also mediates uptake of the anticancer drug cisplatin in yeast and mammals and that decreased CTR1 can result in the development of cisplatin resistance (5,6). Treatment of cancer cells with cisplatin can result in reduced CTR1 expression, which reduces cisplatin accumulation within cells and leads to cisplatin resistance in some human cancer cells (7-9).

$260
100 µl
APPLICATIONS
REACTIVITY
D. melanogaster

Application Methods: Western Blotting

Background: Cell death in the fruit fly Drosophila melanogaster is regulated by many of the same stimuli as mammalian cell death (1). The Drosophila genome contains seven caspase genes; three encode initiator caspases and four encode effector caspases (reviewed in 2). drICE is a cysteine protease that cleaves baculovirus p35 and lamin DmO in vitro and acts downstream of rpr (3). drICE is proteolytically processed during apoptosis into active p21 and p12 subunits. Comparison of the in vivo activity between drICE and Dcp-1 has shown that drICE is a more effective inducer of apoptosis than Dcp-1, which plays a role in determining the rate of cell death (4).

$115
20 µl
$269
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

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

Background: Entry of all eukaryotic cells into mitosis is regulated by activation of cdc2 kinase. The critical regulatory step in activating cdc2 during progression into mitosis appears to be dephosphorylation of Tyr15 and Thr14 (1,2). Phosphorylation at Tyr15 and Thr14 and inhibition of cdc2 is carried out by Wee1 and Myt1 protein kinases, while Tyr15 dephosphorylation and activation of cdc2 is carried out by the cdc25 phosphatase (1,3,4). Hyperphosphorylation and inactivation of Myt1 in mitosis suggests that one or more kinases activated at the G2/M transition negatively regulates Myt1 activity. Kinases shown to phosphorylate Myt1 include cdc2, p90RSK, Akt, and Plk1 (5-8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Troponin, working in conjunction with tropomyosin, functions as a molecular switch that regulates muscle contraction in response to changes in the intracellular Ca2+ concentration. Troponin consists of three subunits: the Ca2+-binding subunit troponin C (TnC), the tropomyosin-binding subunit troponin T (TnT), and the inhibitory subunit troponin I (TnI) (1). In response to β-adrenergic stimulation of the heart, Ser23 and Ser24 of TnI (cardiac) are phosphorylated by PKA and PKC. This phosphorylation stimulates a conformational change of the regulatory domain of TnC, reduces the association between TnI and TnC, and decreases myofilament Ca2+ sensitivity by reducing the Ca2+ binding affinity of TnC (1-3).

$348
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for immunofluorescent analysis in human cells. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated LC3A/B (D3U4C) XP® Rabbit mAb #12741.
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry)

Background: Autophagy is a catabolic process for the autophagosomic-lysosomal degradation of bulk cytoplasmic contents (1,2). Autophagy is generally activated by conditions of nutrient deprivation, but it has also been associated with a number of physiological processes including development, differentiation, neurodegenerative diseases, infection, and cancer (3). Autophagy marker Light Chain 3 (LC3) was originally identified as a subunit of microtubule-associated proteins 1A and 1B (termed MAP1LC3) (4) and subsequently found to contain similarity to the yeast protein Apg8/Aut7/Cvt5 critical for autophagy (5). Three human LC3 isoforms (LC3A, LC3B, and LC3C) undergo post-translational modifications during autophagy (6-9). Cleavage of LC3 at the carboxy terminus immediately following synthesis yields the cytosolic LC3-I form. During autophagy, LC3-I is converted to LC3-II through lipidation by a ubiquitin-like system involving Atg7 and Atg3 that allows for LC3 to become associated with autophagic vesicles (6-10). The presence of LC3 in autophagosomes and the conversion of LC3 to the lower migrating form, LC3-II, have been used as indicators of autophagy (11).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Rab11a, Rab11b, and Rab25 are members of the Rab11 subfamily of small Ras-like GTPases. Unlike universally expressed Rab11, typical Rab25 expression appears to be limited to gastrointestinal mucosa, kidney, and lung (1). Rab25 can associate with apical recycling vesicles to help regulate apical vesicle trafficking (2,3). Research studies indicate that atypical Rab25 expression can be associated with various forms of cancer. Increased Rab25 expression is associated with aggressive growth in ovarian and breast cancer, where Rab25 may inhibit apoptosis and promote cancer cell proliferation and invasion through regulation of vesicle transport and cellular motility (4-7). Interaction between Rab25 and β1 integrin promotes vesicle-mediated transport of integrin to pseudopodial tip membranes, fostering the persistent invasion of tumor cells (8). Conversely, the reported loss of Rab25 expression in a number of breast cancer cases has an unclear effect on cancer pathogenesis (9).

$398
120 slides
1 Kit
The Immunohistochemistry Application Solutions Kit (IHC-P) is designed to conveniently provide supporting reagents needed for immunohistochemistry staining in paraffin-embedded tissue samples or cell pellets (IHC-P). The reagents in this kit are thoroughly validated using our IHC-recommended rabbit polyclonal and monoclonal antibodies and will perform optimally with the CST immunohistochemistry staining protocol, ensuring accurate and reproducible results. This kit includes sufficient reagents for 120 slides based on a 100 µl assay volume. All reagents in this kit are available individually.IMPORTANT: Please refer to the primary antibody data sheet to determine if the antibody is approved for use on paraffin-embedded samples (IHC-P) and for information regarding the appropriate antibody dilution, diluent, and antigen unmasking procedure.
APPLICATIONS

Application Methods: Immunohistochemistry (Paraffin)

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: Members of the Toll-like receptor (TLR) family, named for the closely related Toll receptor in Drosophila, play a pivotal role in innate immune responses (1-4). TLRs recognize conserved motifs found in various pathogens and mediate defense responses (5-7). Triggering of the TLR pathway leads to the activation of NF-κB and subsequent regulation of immune and inflammatory genes (4). The TLRs and members of the IL-1 receptor family share a conserved stretch of approximately 200 amino acids known as the Toll/Interleukin-1 receptor (TIR) domain (1). Upon activation, TLRs associate with a number of cytoplasmic adaptor proteins containing TIR domains, including myeloid differentiation factor 88 (MyD88), MyD88-adaptor-like/TIR-associated protein (MAL/TIRAP), Toll-receptor-associated activator of interferon (TRIF), and Toll-receptor-associated molecule (TRAM) (8-10). This association leads to the recruitment and activation of IRAK1 and IRAK4, which form a complex with TRAF6 to activate TAK1 and IKK (8,11-14). Activation of IKK leads to the degradation of IκB, which normally maintains NF-κB in an inactive state by sequestering it in the cytoplasm.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: Ras-related protein Rab1A (Rab1A) is a member of the Ras superfamily of cellular G proteins that function in protein transport and membrane restructuring (1). Early immunofluorescence studies determined that Rab1A localizes to a region between the endoplasmic reticulum (ER) and the Golgi complex, and in early Golgi compartments (2). Rab1A binds and recruits the COPII complex tethering factor p115 to a cis-SNARE complex associated with COPII-coated, budding vesicles on the endoplasmic reticulum (3). A Rab1 effector complex containing several proteins, including the cis-Golgi tethering protein GM130 and the stacking protein GRASP65, is essential for targeting and fusion of COPII-coated vesicles with the Golgi complex (4). Rab1A also interacts with the golgin tethering and docking proteins giantin (GOLGB1) and golgin-84 to regulate Golgi structure formation and function (5,6). Thus, Rab1A plays an important role in mediating the export of newly synthesized target proteins from ER to the Golgi. As with other Rab proteins, Rab1A function requires an intrinsic GTPase cycling activity facilitated by associated GEF and GAP factors (7-9). In addition to mediating ER to Golgi transport, Rab1A is also involved in autophagy during early autophagosome formation (10,11).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: IQGAPs are scaffolding proteins involved in mediating cytoskeletal function. They contain multiple protein interaction domains and bind to a growing number of molecules including actin, myosin light chain, calmodulin, E-cadherin, and β-catenin (reviewed in 1). Through their GAP-related domains, they bind the small GTPases Rac1 and cdc42. IQGAPs lack GAP activity, however, and regulate small GTPases by stabilizing their GTP-bound (active) forms (2,3). Research studies have shown that the function and distribution of the IQGAP proteins widely vary. IQGAP1 is ubiquitously expressed and has been found to interact with APC (4) and the CLIP170 complex (5) in response to small GTPases, promoting cell polarization and migration. Additional research studies have suggested that IQGAP1 could play a part in the invasiveness of some cancers (6-8). IQGAP2, which is about 60% identical to IQGAP1, is expressed primarily in liver (3), but lower levels have been detected in the prostate, kidney, thyroid, stomach, and testis (9,10). Research studies have shown that IQGAP2 displays tumor suppressor properties (11). Less is known about the function of IQGAP3, but this protein is present in the lung, brain, small intestine, and testis (9) and is only expressed in proliferating cells (12), suggesting a role in cell growth and division.

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

Application Methods: Western Blotting

Background: The Set1 histone methyltransferase protein was first identified in yeast as part of the Set1/COMPASS histone methyltransferase complex, which methylates histone H3 at Lys4 and functions as a transcriptional co-activator (1). While yeast contain only one known Set1 protein, six Set1-related proteins exist in mammals: SET1A, SET1B, MLL1, MLL2, MLL3, and MLL4, all of which assemble into COMPASS-like complexes and methylate histone H3 at Lys4 (2,3). These Set1-related proteins are each found in distinct protein complexes, all of which share the common subunits WDR5, RBBP5, ASH2L, CXXC1 and DPY30. These subunits are required for proper complex assembly and modulation of histone methyltransferase activity (2-6). MLL1 and MLL2 complexes contain the additional protein subunit, menin (6). Like yeast Set1, all six Set1-related mammalian proteins methylate histone H3 at Lys4 (2-6). MLL translocations are found in a large number of hematological malignancies, suggesting that Set1/COMPASS histone methyltransferase complexes play a critical role in leukemogenesis (6).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: DNA topoisomerases I and II are nuclear enzymes; type II consists of two highly homologous isoforms: topoisomerase IIα and IIβ. These enzymes regulate the topology of DNA, maintain genomic integrity, and are essential for processes such as DNA replication, recombination, transcription, and chromosome segregation by allowing DNA strands to pass through each other (1). Topoisomerase I nicks and rejoins one strand of the duplex DNA, while topoisomerase II transiently breaks and closes double-stranded DNA (2). Topoisomerases are very susceptible to various stresses. Acidic pH or oxidative stress can convert topoisomerases to DNA-breaking nucleases, causing genomic instability and cell death. DNA-damaging topoisomerase targeting drugs (e.g., etoposide) also convert topoisomerases to nucleases, with the enzyme usually trapped as an intermediate that is covalently bound to the 5+ end of the cleaved DNA strand(s). Research studies have shown that this intermediate leads to genomic instability and cell death. Thus, agents that target topoisomerases are highly sought after cancer chemotherapeutic drugs (3). Ca2+-regulated phosphorylation of topoisomerase IIα at Ser1106 modulates the activity of this enzyme and its sensitivity to targeting drugs (4).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: Symplekin is necessary for 3’-end cleavage and polyadenylation of mRNAs, histone 3’-end processing and polyadenylation in the cytoplasm (1-5). It is thought to act as a scaffolding protein that brings together factors involved in mRNA 3’-end processing (1,2). Symplekin also plays a role in transcription initiation and termination by RNA polymerase II (RNAPII) through bridging the interaction between the polyadenylation machinery and RNAPII (3,6,7). In addition to its role in mRNA 3’-end processing, research studies have shown that symplekin localizes at epithelial cell tight junctions where it may help to regulate tight junction assembly, thereby maintaining the integrity of the epithelial monolayer and cell polarity (8,9).

$30
25 µl
$107
250 µl
Color-coded Prestained Protein Marker, Low Range (1.7-42 kDa) is a mixture of purified proteins, covalently coupled to blue, green or orange dyes, that resolves to 6 bands between 1.7 and 42 kDa when electrophoresed. The protein concentrations are carefully balanced for even intensity. The covalent coupling of dye to protein affects the electrophoretic mobility in SDS-PAGE gels relative to uncoupled proteins. The apparent molecular weights of the prestained proteins are shown in the gel image.
APPLICATIONS
REACTIVITY
All Species Expected

Application Methods: Western Blotting

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Rat

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

Background: Ring1A plays a role in polycomb group (PcG) protein function. PcG proteins are critically involved in transcriptional repression of Hox genes during development (1,2). PcG proteins form two distinct complexes: EED-EZH2 and the PRC complex, which is composed of at least Bmi1 and Ring1A/Ring1B. The EZH2-containing complex is responsible for the methylation of H3K27, and the PRC complex ubiquitylates H2A. EZH2 methylation is required prior to PRC ubiquitylation, and both are essential for Hox gene repression (3). It has recently been shown that PcG proteins silence a group of developmentally important regulator genes, referred to as bivalent genes (4). This regulation may be responsible for the ability of stem cells to self renew or switch to differentiate into multipotent progenitors. Aberrant epigenetic silencing by PcG proteins is also thought to be important in tumorigenesis (5).

$262
3 nmol
300 µl
SignalSilence® SET8 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit SET8 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 are rigorously tested in-house and have been shown to reduce protein expression by western analysis.
REACTIVITY
Human

Background: SET domain-containing lysine methyltransferase 8 (SET8), also known as PR/SET domain-containing protein 7 (PR/SET7), is a member of a family of histone lysine methyltransferases, each of which contains a conserved catalytic SET domain originally identified in Drosophila Su[var]3-9, Enhancer of zeste, and Trithorax proteins (1-3). SET8 is a single-subunit enzyme that mono-methylates histone H4 on Lys20, preferably on nucleosomal substrates (1-3). SET8 protein levels and Histone H4 Lys20 methylation are cell cycle regulated, both increasing in S phase and peaking at G2/M phase (4,5). SET8 interacts with the PCNA protein, associates with sites of active DNA synthesis, and is required for DNA replication and genome stability during S phase (5-7). Inhibition of SET8 using shRNA or siRNA results in arrest of replication forks, induction of double-stranded DNA breaks, and a Chk1-mediated cell-cycle arrest in S and G2/M phases of the cell cycle (6,7). Furthermore, SET8 methylates p53 on Lys382, down regulating the pro-apoptotic and checkpoint activation functions of p53 (8). In response to DNA damage, SET8 expression levels decrease, allowing p53 to activate checkpoints and/or apoptosis (8). Both the methylation of histone H4 Lys20 and p53 appear to be important for the functions of SET8 in S phase.