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Monkey Ubiquitin Activating Enzyme Activity

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

Application Methods: Immunoprecipitation, Western Blotting

Background: Ubiquitin can be covalently linked to many cellular proteins by the ubiquitination process, which targets proteins for degradation by the 26S proteasome. Three components are involved in the target protein-ubiquitin conjugation process. Ubiquitin is first activated by forming a thioester complex with the ubiquitin-activating enzyme (E1). The activated ubiquitin is subsequently transferred to the ubiquitin-carrier protein E2, and then from E2 to ubiquitin ligase E3 for final delivery to the ε-amino group of the target protein lysine residue (1-3).Ubiquitin-activating enzyme E1-like protein 2/Ubiquitin-like modifier-activating enzyme 6 (UBE1L2/UBA6) is ubiquitously expressed in human tissues and functions as an E1 enzyme related to UBE1/UBA1 (40% identity at the protein level). UBE1L2/UBA6 activates both ubiquitin and the ubiquitin-like protein FAT10 through a similar ATP dependent mechanism (4-6). Like other E1 protein family members, UBE1L2/UBA6 contains a conserved ATP-binding adenylation domain and an active site cysteine residue that are critical for enzymatic function (4,5). Research studies have demonstrated that UBE1L2/UBA6 expression is essential during the early stages of embryogenesis in mice (4). Furthermore, loss of neuronal UBE1L2/UBA6 expression promotes significant defects in neuronal structure and function, which contributes to a reduction in body weight and decreased postnatal viability (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Western Blotting

Background: Interferon-stimulated 15 kDa protein (ISG15), also known as ubiquitin cross-reactive protein (UCRP), is a member of the ubiquitin-like protein family and functions in various biological pathways from pregnancy to innate immune responses (1). Expression of ISG15 is stimulated by cellular exposure to type 1 interferons α and β, in addition to infection with viruses such as influenza B (2,3). After exposure to type I interferons, both lymphocytes and monocytes, in addition to some fibroblasts and epithelial cells, release ISG15 into culture medium (1,4). ISG15 has been shown to function as a cytokine, stimulating interferon γ secretion by monocytes and macrophages, proliferation of natural killer cells, and chemotactic responses in neutrophils (4,5). ISG15 has also been shown to function intracellularly, being covalently conjugated to other proteins by E1 (Ube1L), E2 (UbcH8) and E3 ligases via a multi-step process analogous to ubiquitination (6,7). ISG15 is removed from proteins by the ubiquitin processing protease Ubp43 (8). ISG15-protein conjugation (ISGylation) is induced by type 1 interferons, and target proteins include the serine protease inhibitor Serpin 2A, PLCγ1, ERK1/2, Jak1 and Stat1 (9,10). Unlike ubiquitination, ISGylation does not target proteins for degradation, rather ISGylation increases Jak1 and Stat1 activity, enhancing the cellular response to interferons (11).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: The process of SUMO conjugation to target proteins is similar to the molecular chain of events observed with ubiquitin (1). SUMO is conjugated to target proteins through the coordinated action of the cellular SUMO conjugation machinery, which consists of the E1, E2, and E3 enzymes (2). The canonical SUMO E1 activating enzyme is a heterodimer consisting of Ubiquitin-like 1-activating enzyme E1A (UBLE1A, SAE1) and UBLE1B (SAE2, UBA2) subunits. Mature SUMO is activated by E1 in an ATP-dependent reaction that generates adenylated SUMO, which functions as a high-energy intermediate in the formation of a thioester linkage between SUMO and Cys173 of SAE2 (3,4). SUMO is subsequently transferred from SAE2 to the SUMO E2 conjugating enzyme UBE2I (5). Research studies indicate that UBLE1A (SAE1) is a nuclear protein and c-Myc transcriptional target whose expression is required for Myc-driven tumorigenesis (6-8).

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

Application Methods: Western Blotting

Background: Similar to ubiquitin, NEDD8 is covalently linked to target proteins through an enzymatic cascade composed of NEDD8-specific E1 (activating)- and E2 (conjugating)-enzymes (1,2). The E2 ligase specific for NEDD8 is Ubc12 (3-5). Ubc12 forms a heterodimeric conjugate with NEDD8 in order to catalyze the transfer of NEDD8 from E1 to lysine side chains of target proteins (1,2). Well known targets of NEDD8 are cullin-based RING E3 ligases. Neddylation of cullin isoforms activates the related ubiquitin E3 complex by promoting its interaction with a cognate ubiquitin-E2 ligase (6-7). Neddylation of Cul-1 complexes containing βTrCP and SKP2 has been shown to be required for controlling the stability of important signaling targets such as IκB, NF-κB, and p27 Kip (8-10), thereby regulating cell cycle progression, signaling cascades, and developmental programming processes (11).

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

Application Methods: Western Blotting

Background: Activation of protein kinase C (PKC) is one of the earliest events in a cascade that controls a variety of cellular responses, including secretion, gene expression, proliferation, and muscle contraction (1,2). PKC isoforms belong to three groups based on calcium dependency and activators. Classical PKCs are calcium-dependent via their C2 domains and are activated by phosphatidylserine (PS), diacylglycerol (DAG), and phorbol esters (TPA, PMA) through their cysteine-rich C1 domains. Both novel and atypical PKCs are calcium-independent, but only novel PKCs are activated by PS, DAG, and phorbol esters (3-5). Members of these three PKC groups contain a pseudo-substrate or autoinhibitory domain that binds to substrate-binding sites in the catalytic domain to prevent activation in the absence of cofactors or activators. Control of PKC activity is regulated through three distinct phosphorylation events. Phosphorylation occurs in vivo at Thr500 in the activation loop, at Thr641 through autophosphorylation, and at the carboxy-terminal hydrophobic site Ser660 (2). Atypical PKC isoforms lack hydrophobic region phosphorylation, which correlates with the presence of glutamic acid rather than the serine or threonine residues found in more typical PKC isoforms. The enzyme PDK1 or a close relative is responsible for PKC activation. A recent addition to the PKC superfamily is PKCμ (PKD), which is regulated by DAG and TPA through its C1 domain. PKD is distinguished by the presence of a PH domain and by its unique substrate recognition and Golgi localization (6). PKC-related kinases (PRK) lack the C1 domain and do not respond to DAG or phorbol esters. Phosphatidylinositol lipids activate PRKs, and small Rho-family GTPases bind to the homology region 1 (HR1) to regulate PRK kinase activity (7).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: Activation of protein kinase C (PKC) is one of the earliest events in a cascade that controls a variety of cellular responses, including secretion, gene expression, proliferation, and muscle contraction (1,2). PKC isoforms belong to three groups based on calcium dependency and activators. Classical PKCs are calcium-dependent via their C2 domains and are activated by phosphatidylserine (PS), diacylglycerol (DAG), and phorbol esters (TPA, PMA) through their cysteine-rich C1 domains. Both novel and atypical PKCs are calcium-independent, but only novel PKCs are activated by PS, DAG, and phorbol esters (3-5). Members of these three PKC groups contain a pseudo-substrate or autoinhibitory domain that binds to substrate-binding sites in the catalytic domain to prevent activation in the absence of cofactors or activators. Control of PKC activity is regulated through three distinct phosphorylation events. Phosphorylation occurs in vivo at Thr500 in the activation loop, at Thr641 through autophosphorylation, and at the carboxy-terminal hydrophobic site Ser660 (2). Atypical PKC isoforms lack hydrophobic region phosphorylation, which correlates with the presence of glutamic acid rather than the serine or threonine residues found in more typical PKC isoforms. The enzyme PDK1 or a close relative is responsible for PKC activation. A recent addition to the PKC superfamily is PKCμ (PKD), which is regulated by DAG and TPA through its C1 domain. PKD is distinguished by the presence of a PH domain and by its unique substrate recognition and Golgi localization (6). PKC-related kinases (PRK) lack the C1 domain and do not respond to DAG or phorbol esters. Phosphatidylinositol lipids activate PRKs, and small Rho-family GTPases bind to the homology region 1 (HR1) to regulate PRK kinase activity (7).

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

Application Methods: Western Blotting

Background: Activation of protein kinase C (PKC) is one of the earliest events in a cascade that controls a variety of cellular responses, including secretion, gene expression, proliferation, and muscle contraction (1,2). PKC isoforms belong to three groups based on calcium dependency and activators. Classical PKCs are calcium-dependent via their C2 domains and are activated by phosphatidylserine (PS), diacylglycerol (DAG), and phorbol esters (TPA, PMA) through their cysteine-rich C1 domains. Both novel and atypical PKCs are calcium-independent, but only novel PKCs are activated by PS, DAG, and phorbol esters (3-5). Members of these three PKC groups contain a pseudo-substrate or autoinhibitory domain that binds to substrate-binding sites in the catalytic domain to prevent activation in the absence of cofactors or activators. Control of PKC activity is regulated through three distinct phosphorylation events. Phosphorylation occurs in vivo at Thr500 in the activation loop, at Thr641 through autophosphorylation, and at the carboxy-terminal hydrophobic site Ser660 (2). Atypical PKC isoforms lack hydrophobic region phosphorylation, which correlates with the presence of glutamic acid rather than the serine or threonine residues found in more typical PKC isoforms. The enzyme PDK1 or a close relative is responsible for PKC activation. A recent addition to the PKC superfamily is PKCμ (PKD), which is regulated by DAG and TPA through its C1 domain. PKD is distinguished by the presence of a PH domain and by its unique substrate recognition and Golgi localization (6). PKC-related kinases (PRK) lack the C1 domain and do not respond to DAG or phorbol esters. Phosphatidylinositol lipids activate PRKs, and small Rho-family GTPases bind to the homology region 1 (HR1) to regulate PRK kinase activity (7).

$122
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat, Xenopus

Application Methods: Immunohistochemistry (Paraffin), Western Blotting

Background: Activation of protein kinase C (PKC) is one of the earliest events in a cascade that controls a variety of cellular responses, including secretion, gene expression, proliferation, and muscle contraction (1,2). PKC isoforms belong to three groups based on calcium dependency and activators. Classical PKCs are calcium-dependent via their C2 domains and are activated by phosphatidylserine (PS), diacylglycerol (DAG), and phorbol esters (TPA, PMA) through their cysteine-rich C1 domains. Both novel and atypical PKCs are calcium-independent, but only novel PKCs are activated by PS, DAG, and phorbol esters (3-5). Members of these three PKC groups contain a pseudo-substrate or autoinhibitory domain that binds to substrate-binding sites in the catalytic domain to prevent activation in the absence of cofactors or activators. Control of PKC activity is regulated through three distinct phosphorylation events. Phosphorylation occurs in vivo at Thr500 in the activation loop, at Thr641 through autophosphorylation, and at the carboxy-terminal hydrophobic site Ser660 (2). Atypical PKC isoforms lack hydrophobic region phosphorylation, which correlates with the presence of glutamic acid rather than the serine or threonine residues found in more typical PKC isoforms. The enzyme PDK1 or a close relative is responsible for PKC activation. A recent addition to the PKC superfamily is PKCμ (PKD), which is regulated by DAG and TPA through its C1 domain. PKD is distinguished by the presence of a PH domain and by its unique substrate recognition and Golgi localization (6). PKC-related kinases (PRK) lack the C1 domain and do not respond to DAG or phorbol esters. Phosphatidylinositol lipids activate PRKs, and small Rho-family GTPases bind to the homology region 1 (HR1) to regulate PRK kinase activity (7).

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

Application Methods: 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).

$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, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: Protein ubiquitination requires the concerted action of the E1, E2, and E3 ubiquitin-conjugating enzymes. Ubiquitin is first activated through ATP-dependent formation of a thiol ester with ubiquitin-activating enzyme E1. The activated ubiquitin is then transferred to a thiol group of ubiquitin-carrier enzyme E2. The final step is the transfer of ubiquitin from E2 to an ε-amino group of the target protein lysine residue, which is mediated by ubiquitin-ligase enzyme E3 (1).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: Protein ubiquitination requires the concerted action of the E1, E2, and E3 ubiquitin-conjugating enzymes. Ubiquitin is first activated through ATP-dependent formation of a thiol ester with ubiquitin-activating enzyme E1. The activated ubiquitin is then transferred to a thiol group of ubiquitin-carrier enzyme E2. The final step is the transfer of ubiquitin from E2 to an ε-amino group of the target protein lysine residue, which is mediated by ubiquitin-ligase enzyme E3 (1).

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

Application Methods: Western Blotting

Background: The E3 ubiquitin-protein ligase ARIH2 (TRIAD1) is an Ariadne subfamily ligase involved in the polyubiquitination of proteins designated for proteasomal degradation. The TRIAD1 nuclear protein contains an amino-terminal acidic region, a pair of RING fingers, two carboxyl-terminal coiled coil domains and a novel C6HC DRIL/IBR domain located between the RING fingers. Together, the paired RING fingers and DRIL/IBR domain form a highly conserved TRIAD (two RING fingers and DRIL) domain (1). Research studies suggest that TRIAD1 mediates both Lys48 and Lys63 protein polyubiquitination and acts as a negative regulator of myelopoiesis. TRIAD1 ubiquitin ligase inhibits myeloid cell proliferation by mediating protein ubiquitination through the ubiquitin-conjugating enzymes UbcH7 and UbcH13 (2,3). Experimental deletion of TRIAD1 in mice has a lethal effect, leading to death at the embryonic stage or later due to a severe, multi-organ inflammatory response. Results indicate that TRIAD1 binds IκBβ in dendritic cells and promotes the degradation of the NF-κB inhibitor (4).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: The carboxy terminus of Hsc70-interacting protein (CHIP, STUB1) is a co-chaperone protein and functional E3 ubiquitin ligase that links the polypeptide binding activity of Hsp70 to the ubiquitin proteasome system (1). Cytoplasmic CHIP protein contains three 34-amino acid TPR (tetratricopeptide repeat) domains at its amino terminus and a carboxy-terminal U-box domain. CHIP interacts with the molecular chaperones Hsc70-Hsp70 and Hsp90 through its TPR domain, while E3 ubiquitin ligase activity is confined to the U-box domain (2,3). The binding of CHIP to Hsp70 can stall the folding of Hsp70 client proteins and concomitantly facilitate the U-box dependent ubiquitination of Hsp70-bound substrates (4-6). CHIP appears to play a central role in cell stress protection (7) and is responsible for the degradation of disease-related proteins that include cystic fibrosis transmembrane conductance regulator (4), p53 (8), huntingtin and Ataxin-3 (9), Tau protein (10), and α-synuclein (11).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: 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
Bovine, Human, Monkey, Mouse, Pig, Rat

Application Methods: Western Blotting

Background: HSPA8, alternately known as HSC70 or HSP73, is a constitutively expressed member of the HSP70 superfamily (1). Although its primary role in cells appears to be that of a general chaperone for unfolded proteins, HSPA8 has also been identified as the uncoating ATPase responsible for removing clathrin from coated vesicles and may also play a role in stabilizing untranslated mRNAs (1-5). In addition to these "housekeeping" functions, HSPA8 may also have an important role in inducible cellular stress responses. For example, oxidative or thermal stress promotes the nuclear/nucleolar accumulation of HSPA8, where it forms a complex with the topoisomerase I complex and likely protects it from heat inactivation (6,7). HSPA8 is reportedly phosphorylated in response to DNA damage, but it remains unclear what effect, if any, this has on HSPA8 function (8-10). Numerous high throughput studies support this observation. For more information, please see the HSPA8 page in PhosphoSitePlus® at www.phosphosite.org.

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

Application Methods: Immunoprecipitation, Western Blotting

Background: Arrestin proteins function as negative regulators of G protein-coupled receptor (GPCR) signaling. Cognate ligand binding stimulates GPCR phosphorylation, which is followed by binding of arrestin to the phosphorylated GPCR and the eventual internalization of the receptor and desensitization of GPCR signaling (1). Four distinct mammalian arrestin proteins are known. Arrestin 1 (also known as S-arrestin) and arrestin 4 (X-arrestin) are localized to retinal rods and cones, respectively. Arrestin 2 (also known as β-arrestin 1) and arrestin 3 (β-arrestin 2) are ubiquitously expressed and bind to most GPCRs (2). β-arrestins function as adaptor and scaffold proteins and play important roles in other processes, such as recruiting c-Src family proteins to GPCRs in Erk activation pathways (3,4). β-arrestins are also involved in some receptor tyrosine kinase signaling pathways (5-8). Additional evidence suggests that β-arrestins translocate to the nucleus and help regulate transcription by binding transcriptional cofactors (9,10).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: Protein ubiquitination and deubiquitination are reversible processes catalyzed by ubiquitinating enzymes and deubiquitinating enzymes, respectively (1,2). Deubiquitinating enzymes (DUBs) are categorized into five subfamilies based on catalytic domain structure: USP, OTU, MJD, UCH, and JAMM/MPN. BRCC36 is a zinc-dependent DUB belonging to the JAMM/MPN subfamily and participates in DNA damage responses and interferon signaling by specifically catalyzing hydrolysis of K63-linked polyubiquitin chains (3,4). In the nucleus, BRCC36 is part of the BRCA1-A complex that contains RAP80, BRCA1, ABRAXAS, and MERIT40 (5,6). This complex plays a critical role in mediating the cellular repair of DNA double strand breaks induced by ionizing radiation (7-10). Research studies have shown that BRCC36 is overexpressed in a high percentage of breast tumors, which may contribute to resistance of breast cancer cells to ionizing radiation-induced apoptosis (4). BRCC36 also functions in the cytoplasm as part of a distinct complex known as the BRCC36-containing isopeptide complex (BRISC) (5,6). Indeed, research studies have shown that BRCC36 deubquitinates and stabilizes IFNAR1 to modulate the cellular response to interferons (3).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Bovine, Human, Monkey, Mouse, Rat

Application Methods: Immunohistochemistry (Paraffin), Western Blotting

Background: HSP70 and HSP90 are molecular chaperones expressed constitutively under normal conditions to maintain protein homeostasis and are induced upon environmental stress (1). Both HSP70 and HSP90 are able to interact with unfolded proteins to prevent irreversible aggregation and catalyze the refolding of their substrates in an ATP- and co-chaperone-dependent manner (1). HSP70 has a broad range of substrates including newly synthesized and denatured proteins, while HSP90 tends to have a more limited subset of substrates, most of which are signaling molecules. HSP70 and HSP90 often function collaboratively in a multi-chaperone system, which requires a minimal set of co-chaperones: HSP40, Hop, and p23 (2,3). The co-chaperones either regulate the intrinsic ATPase activity of the chaperones or recruit chaperones to specific substrates or subcellular compartments (1,4). When the ubiquitin ligase CHIP associates with the HSP70/HSP90 complex as a cofactor, the unfolded substrates are subjected to degradation by the proteasome (4). The biological functions of HSP70/HSP90 extend beyond their chaperone activity. They are essential for the maturation and inactivation of nuclear hormones and other signaling molecules (1,3). They also play a role in vesicle formation and protein trafficking (2).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

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

Background: HSP70 and HSP90 are molecular chaperones expressed constitutively under normal conditions to maintain protein homeostasis and are induced upon environmental stress (1). Both HSP70 and HSP90 are able to interact with unfolded proteins to prevent irreversible aggregation and catalyze the refolding of their substrates in an ATP- and co-chaperone-dependent manner (1). HSP70 has a broad range of substrates including newly synthesized and denatured proteins, while HSP90 tends to have a more limited subset of substrates, most of which are signaling molecules. HSP70 and HSP90 often function collaboratively in a multi-chaperone system, which requires a minimal set of co-chaperones: HSP40, Hop, and p23 (2,3). The co-chaperones either regulate the intrinsic ATPase activity of the chaperones or recruit chaperones to specific substrates or subcellular compartments (1,4). When the ubiquitin ligase CHIP associates with the HSP70/HSP90 complex as a cofactor, the unfolded substrates are subjected to degradation by the proteasome (4). The biological functions of HSP70/HSP90 extend beyond their chaperone activity. They are essential for the maturation and inactivation of nuclear hormones and other signaling molecules (1,3). They also play a role in vesicle formation and protein trafficking (2).