CDC37

Summary

Gene Symbol: CDC37
Description: cell division cycle 37
Alias: P50CDC37, hsp90 co-chaperone Cdc37, CDC37 (cell division cycle 37, S. cerevisiae, homolog), CDC37 cell division cycle 37 homolog, cell division cycle 37 homolog, hsp90 chaperone protein kinase-targeting subunit
Species: human
Products:     CDC37

Top Publications

  1. Schwarze S, Fu V, Jarrard D. Cdc37 enhances proliferation and is necessary for normal human prostate epithelial cell survival. Cancer Res. 2003;63:4614-9 pubmed
    b>Cdc37 is a co-chaperone protein that recruits several immature client kinases to Hsp90 for proper folding. Cdc37 up-regulation is a common early event in localized human prostate cancer...
  2. Moriwaki Y, Kim Y, Ido Y, Misawa H, Kawashima K, Endo S, et al. L347P PINK1 mutant that fails to bind to Hsp90/Cdc37 chaperones is rapidly degraded in a proteasome-dependent manner. Neurosci Res. 2008;61:43-8 pubmed publisher
    ..Here we report that PINK1 forms a complex with the molecular chaperones Hsp90 and Cdc37/p50 within cells, which appears to enhance its stability...
  3. Xu W, Mollapour M, Prodromou C, Wang S, Scroggins B, Palchick Z, et al. Dynamic tyrosine phosphorylation modulates cycling of the HSP90-P50(CDC37)-AHA1 chaperone machine. Mol Cell. 2012;47:434-43 pubmed publisher
    ..After initially forming a ternary complex with kinase client and the cochaperone p50(Cdc37), Hsp90 proceeds through a cycle of conformational changes facilitated by ATP binding and hydrolysis...
  4. Stepanova L, Leng X, Parker S, Harper J. Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev. 1996;10:1491-502 pubmed
    ..We have identified mammalian p50Cdc37 as a protein kinase-targeting subunit of the molecular chaperone Hsp90...
  5. Lamphere L, Fiore F, Xu X, Brizuela L, Keezer S, Sardet C, et al. Interaction between Cdc37 and Cdk4 in human cells. Oncogene. 1997;14:1999-2004 pubmed
    ..Here we described the interaction of Cdk4 with a human homologue of the yeast Drosophila CDC37 gene products...
  6. Hartson S, Irwin A, Shao J, Scroggins B, Volk L, Huang W, et al. p50(cdc37) is a nonexclusive Hsp90 cohort which participates intimately in Hsp90-mediated folding of immature kinase molecules. Biochemistry. 2000;39:7631-44 pubmed
    Hsp90 and p50(cdc37) provide a poorly understood biochemical function essential to certain protein kinases, and recent models describe p50(cdc37) as an exclusive hsp90 cohort which links hsp90 machinery to client kinases...
  7. Basso A, Solit D, Chiosis G, Giri B, Tsichlis P, Rosen N. Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function. J Biol Chem. 2002;277:39858-66 pubmed
    ..Intracellular Akt is associated with Hsp90 and Cdc37 in a complex in which Akt kinase is active and regulated by phosphatidylinositol 3-kinase...
  8. Miyata Y, Nishida E. CK2 controls multiple protein kinases by phosphorylating a kinase-targeting molecular chaperone, Cdc37. Mol Cell Biol. 2004;24:4065-74 pubmed
    b>Cdc37 is a kinase-associated molecular chaperone whose function in concert with Hsp90 is essential for many signaling protein kinases. Here, we report that mammalian Cdc37 is a pivotal substrate of CK2 (casein kinase II)...
  9. da Rocha Dias S, Friedlos F, Light Y, Springer C, Workman P, Marais R. Activated B-RAF is an Hsp90 client protein that is targeted by the anticancer drug 17-allylamino-17-demethoxygeldanamycin. Cancer Res. 2005;65:10686-91 pubmed
    ..Our data show that B-RAF is an important target for 17-AAG in human cancer. ..

More Information

Publications121 found, 100 shown here

  1. Kimura Y, Rutherford S, Miyata Y, Yahara I, Freeman B, Yue L, et al. Cdc37 is a molecular chaperone with specific functions in signal transduction. Genes Dev. 1997;11:1775-85 pubmed
    b>Cdc37 is required for cyclin-dependent kinase activation and is genetically linked with the activity of several other kinases, including oncogenic v-Src, casein kinase II, MPS-1 kinase, and sevenless...
  2. Grammatikakis N, Lin J, Grammatikakis A, Tsichlis P, Cochran B. p50(cdc37) acting in concert with Hsp90 is required for Raf-1 function. Mol Cell Biol. 1999;19:1661-72 pubmed
    Genetic screens in Drosophila have identified p50(cdc37) to be an essential component of the sevenless receptor/mitogen-activated kinase protein (MAPK) signaling pathway, but neither the function nor the target of p50(cdc37) in this ..
  3. Chen G, Cao P, Goeddel D. TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90. Mol Cell. 2002;9:401-10 pubmed
    ..We identify Cdc37 and Hsp90 as two additional components of the IKK complex...
  4. Lavictoire S, Parolin D, Klimowicz A, Kelly J, Lorimer I. Interaction of Hsp90 with the nascent form of the mutant epidermal growth factor receptor EGFRvIII. J Biol Chem. 2003;278:5292-9 pubmed
    ..The Hsp90-associated chaperone Cdc37 also co-purified with EGFRvIII, suggesting that Hsp90 binds EGFRvIII as a complex with this protein...
  5. Vaughan C, Gohlke U, Sobott F, Good V, Ali M, Prodromou C, et al. Structure of an Hsp90-Cdc37-Cdk4 complex. Mol Cell. 2006;23:697-707 pubmed
    ..Recruitment of protein kinase clients to the Hsp90 chaperone system is mediated by the cochaperone adaptor protein Cdc37, which acts as a scaffold, simultaneously binding protein kinases and Hsp90...
  6. Hinz M, Broemer M, Arslan S, Otto A, Mueller E, Dettmer R, et al. Signal responsiveness of IkappaB kinases is determined by Cdc37-assisted transient interaction with Hsp90. J Biol Chem. 2007;282:32311-9 pubmed
    ..Heat shock protein 90 (Hsp90) and the co-chaperone Cdc37 have been indicated as additional subunits, but their specific functions in signal transduction are indistinct...
  7. Wang L, Xie C, Greggio E, Parisiadou L, Shim H, Sun L, et al. The chaperone activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2. J Neurosci. 2008;28:3384-91 pubmed publisher
    ..Therefore, inhibition of LRRK2 kinase activity can be achieved by blocking Hsp90-mediated chaperone activity and Hsp90 inhibitors may serve as potential anti-PD drugs. ..
  8. Nichols R, Dzamko N, Morrice N, Campbell D, Deak M, Ordureau A, et al. 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization. Biochem J. 2010;430:393-404 pubmed publisher
    ..These results provide the first evidence suggesting that 14-3-3 regulates LRRK2 and that disruption of the interaction of LRRK2 with 14-3-3 may be linked to Parkinson's disease...
  9. Shao J, Grammatikakis N, Scroggins B, Uma S, Huang W, Chen J, et al. Hsp90 regulates p50(cdc37) function during the biogenesis of the activeconformation of the heme-regulated eIF2 alpha kinase. J Biol Chem. 2001;276:206-14 pubmed
    Recent studies indicate that p50(cdc37) facilitates Hsp90-mediated biogenesis of certain protein kinases...
  10. Zhao Q, Boschelli F, Caplan A, Arndt K. Identification of a conserved sequence motif that promotes Cdc37 and cyclin D1 binding to Cdk4. J Biol Chem. 2004;279:12560-4 pubmed
    b>Cdc37 is a molecular chaperone that is important for the stability and activity of several protein kinases, including Cdk4 and Raf1. We first determined, using in vitro assays, that Cdc37 binds to the amino-terminal lobe of Cdk4...
  11. Roe S, Ali M, Meyer P, Vaughan C, Panaretou B, Piper P, et al. The Mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(cdc37). Cell. 2004;116:87-98 pubmed
    Recruitment of protein kinase clients to the Hsp90 chaperone involves the cochaperone p50(cdc37) acting as a scaffold, binding protein kinases via its N-terminal domain and Hsp90 via its C-terminal region...
  12. Roiniotis J, Masendycz P, Ho S, Scholz G. Domain-mediated dimerization of the Hsp90 cochaperones Harc and Cdc37. Biochemistry. 2005;44:6662-9 pubmed
    ..The novel Hsp90 cochaperone Harc was identified previously on the basis of its amino acid sequence similarity to Cdc37. Although the biochemical role of Harc has not been established, the structural similarities between Harc and ..
  13. Smith J, Clarke P, de Billy E, Workman P. Silencing the cochaperone CDC37 destabilizes kinase clients and sensitizes cancer cells to HSP90 inhibitors. Oncogene. 2009;28:157-69 pubmed publisher
    The cochaperone CDC37 promotes the association of HSP90 with the protein kinase subset of client proteins to maintain their stability and signalling functions...
  14. Wang H, Goode T, Iakova P, Albrecht J, Timchenko N. C/EBPalpha triggers proteasome-dependent degradation of cdk4 during growth arrest. EMBO J. 2002;21:930-41 pubmed
    ..Gel filtration analysis of cdk4 complexes shows that a chaperone complex cdk4-cdc37-Hsp90, which protects cdk4 from degradation, is abundant in proliferating livers that lack C/EBPalpha, but this ..
  15. Siligardi G, Panaretou B, Meyer P, Singh S, Woolfson D, Piper P, et al. Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37. J Biol Chem. 2002;277:20151-9 pubmed
    ..of protein kinase clients to the Hsp90 complex appears to involve a specialized co-chaperone, Cdc37p/p50(cdc37), whose binding to Hsp90 is mutually exclusive of Sti1/Hop/p60...
  16. Gray P, Stevenson M, Calderwood S. Targeting Cdc37 inhibits multiple signaling pathways and induces growth arrest in prostate cancer cells. Cancer Res. 2007;67:11942-50 pubmed
    ..An important intracellular cofactor for HSP90 is Cdc37, a protein with a broad role in fostering the activities of protein kinases...
  17. Silverstein A, Grammatikakis N, Cochran B, Chinkers M, Pratt W. p50(cdc37) binds directly to the catalytic domain of Raf as well as to a site on hsp90 that is topologically adjacent to the tetratricopeptide repeat binding site. J Biol Chem. 1998;273:20090-5 pubmed
    ..with hsp90 and a 50-kDa protein that is the mammalian homolog of the yeast cell cycle control protein Cdc37. In contrast, unliganded steroid receptors exist in heterocomplexes with hsp90 and a tetratricopeptide repeat (TPR)..
  18. Weihofen A, Ostaszewski B, Minami Y, Selkoe D. Pink1 Parkinson mutations, the Cdc37/Hsp90 chaperones and Parkin all influence the maturation or subcellular distribution of Pink1. Hum Mol Genet. 2008;17:602-16 pubmed
    ..complexes by mass spectrometry, co-immunoprecipitation and Hsp90 inhibitor studies, we identify Pink1 as a novel Cdc37/Hsp90 client kinase...
  19. Shao J, Prince T, Hartson S, Matts R. Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. J Biol Chem. 2003;278:38117-20 pubmed
    The Hsp90 co-chaperone Cdc37 provides an essential function for the biogenesis and support of numerous protein kinases...
  20. Sun Y, Zhai L, Ma S, Zhang C, Zhao L, Li N, et al. Down-regulation of RIP3 potentiates cisplatin chemoresistance by triggering HSP90-ERK pathway mediated DNA repair in esophageal squamous cell carcinoma. Cancer Lett. 2018;418:97-108 pubmed publisher
    ..Functional studies showed that deficient RIP3 upregulated FOSL1 and POLD1 through activation of the HSP90/CDC37 complex and ERK phosphorylation in multiple cell lines...
  21. Mbonye U, Wang B, Gokulrangan G, Shi W, Yang S, Karn J. Cyclin-dependent kinase 7 (CDK7)-mediated phosphorylation of the CDK9 activation loop promotes P-TEFb assembly with Tat and proviral HIV reactivation. J Biol Chem. 2018;293:10009-10025 pubmed publisher
    ..that disrupted CDK9/CycT1 assembly accumulated Thr-186-dephosphorylated CDK9 associated with the cytoplasmic Hsp90/Cdc37 chaperone. The Hsp90/Cdc37/CDK9 complex was also present in resting T cells, which lack CycT1...
  22. Bryan K, Jarboui M, Raso C, Bernal Llinares M, McCann B, Rauch J, et al. HiQuant: Rapid Postquantification Analysis of Large-Scale MS-Generated Proteomics Data. J Proteome Res. 2016;15:2072-9 pubmed publisher
    ..Download HiQuant, sample data sets, and supporting documentation at http://hiquant.primesdb.eu . ..
  23. Obermann W. A motif in HSP90 and P23 that links molecular chaperones to efficient estrogen receptor α methylation by the lysine methyltransferase SMYD2. J Biol Chem. 2018;293:16479-16487 pubmed publisher
    ..Co-chaperones such as P23, cell division cycle 37 (CDC37), or activator of HSP90 ATPase activity 1 (AHA1) interact with the N-terminal or middle domain of HSP90, whereas ..
  24. Park S, Dong B, Matsumura F. Rapid activation of c-Src kinase by dioxin is mediated by the Cdc37-HSP90 complex as part of Ah receptor signaling in MCF10A cells. Biochemistry. 2007;46:899-908 pubmed
    ..within 10-30 min of the addition of TCDD, is also accompanied by simultaneous translocation of both Src and cdc37 proteins from cytosol into the 100,000 x g membrane fraction containing the plasma membrane...
  25. El Hamidieh A, Grammatikakis N, Patsavoudi E. Cell surface Cdc37 participates in extracellular HSP90 mediated cancer cell invasion. PLoS ONE. 2012;7:e42722 pubmed publisher
    b>Cdc37 is a 50 kDa molecular chaperone which targets intrinsically unstable protein kinases to the molecular chaperone HSP90...
  26. Guerra B, Rasmussen T, Schnitzler A, Jensen H, Boldyreff B, Miyata Y, et al. Protein kinase CK2 inhibition is associated with the destabilization of HIF-1α in human cancer cells. Cancer Lett. 2015;356:751-61 pubmed publisher
    ..apoptotic cell death in various cancer cell lines and upon hypoxia, the compound suppresses CK2-catalyzed HSP90/Cdc37 phosphorylation and induces HIF-1α degradation...
  27. Li T, Jiang H, Tong Y, Lu J. Targeting the Hsp90-Cdc37-client protein interaction to disrupt Hsp90 chaperone machinery. J Hematol Oncol. 2018;11:59 pubmed publisher
    ..With the roles of Hsp90 co-chaperones being elucidated, cell division cycle 37 (Cdc37), a ubiquitous co-chaperone of Hsp90 that directs the selective client proteins into the Hsp90 chaperone cycle, ..
  28. Yang C, Wang H, Zhu D, Hong C, Dmitriev P, Zhang C, et al. Mutant glucocerebrosidase in Gaucher disease recruits Hsp27 to the Hsp90 chaperone complex for proteasomal degradation. Proc Natl Acad Sci U S A. 2015;112:1137-42 pubmed publisher
    ..In the present study, we demonstrate that the Hsp90/HOP/Cdc37 complex recruits Hsp27 after recognition of GCase mutants with subsequent targeting of GCase mutant peptides to ..
  29. Nakamoto H, Amaya Y, Komatsu T, Suzuki T, Dohmae N, Nakamura Y, et al. Stimulation of the ATPase activity of Hsp90 by zerumbone modification of its cysteine residues destabilizes its clients and causes cytotoxicity. Biochem J. 2018;475:2559-2576 pubmed publisher
    ..In addition, zerumbone inhibited the binding of Hsp90/Cdc37 to client kinases...
  30. Ota A, Wang Y. Cdc37/Hsp90 protein-mediated regulation of IRE1α protein activity in endoplasmic reticulum stress response and insulin synthesis in INS-1 cells. J Biol Chem. 2012;287:6266-74 pubmed publisher
    ..Here, we report that the Hsp90 cochaperone Cdc37 directly interacts with IRE1α through a highly conserved cytosolic motif of IRE1α...
  31. Khattar V, Fried J, Xu B, Thottassery J. Cks1 proteasomal degradation is induced by inhibiting Hsp90-mediated chaperoning in cancer cells. Cancer Chemother Pharmacol. 2015;75:411-20 pubmed publisher
    ..Cks1 is known to interact with the Hsp90-Cdc37 chaperone machinery, although whether this facilitates its conformational maturation and stability is not known...
  32. Pan T, Peng Z, Tan L, Zou F, Zhou N, Liu B, et al. Nonsteroidal Anti-inflammatory Drugs Potently Inhibit the Replication of Zika Viruses by Inducing the Degradation of AXL. J Virol. 2018;92: pubmed publisher
    ..E receptor 2 (EP2)/cAMP/protein kinase A (PKA) signaling pathway and reduced PKA-dependent CDC37 phosphorylation and the interaction between CDC37 and HSP90, which subsequently facilitated CHIP/ubiquitination/..
  33. Manjarrez J, Sun L, Prince T, Matts R. Hsp90-dependent assembly of the DBC2/RhoBTB2-Cullin3 E3-ligase complex. PLoS ONE. 2014;9:e90054 pubmed publisher
    ..k.a RhoBTB2) is suppressed in many cancers, in addition to breast cancer. In a screen for Cdc37-associated proteins, DBC2 was identified to be a potential client protein of the 90 kDa heat shock protein (Hsp90) ..
  34. He Y, Fang J, Xue L, Wu J, Dawar F, Mei J. Potential contributions of heat shock proteins and related genes in sexual differentiation in yellow catfish (Pelteobagrus fulvidraco). Fish Physiol Biochem. 2017;43:465-475 pubmed publisher
    ..All these genes were sex-biased expressed in gonads. Hspa5, Hip, and Cdc37 were expressed more highly in ovary than in testis, whereas Hsp90?, Hspb2, Hspb8, and Hspbp1 were expressed more ..
  35. Thurm C, Poltorak M, Reimer E, Brinkmann M, Leichert L, Schraven B, et al. A highly conserved redox-active Mx(2)CWx(6)R motif regulates Zap70 stability and activity. Oncotarget. 2017;8:30805-30816 pubmed publisher
    ..A C575A substitution results in protein instability, reduced activity, and increased dependency on the Hsp90/Cdc37 chaperone system...
  36. Yamamoto T, Wang L, Fisher L, Eckerdt F, Peng A. Regulation of Greatwall kinase by protein stabilization and nuclear localization. Cell Cycle. 2014;13:3565-75 pubmed publisher
    ..In this study we identified Hsp90, Cdc37 and members of the importin α and β families as the major binding partners of Gwl...
  37. Calderwood S. Cdc37 as a co-chaperone to Hsp90. Subcell Biochem. 2015;78:103-12 pubmed publisher
    The co-chaperone p50/Cdc37 is an important partner for Hsp90, assisting in molecular chaperone activities, particularly with regard to the regulation of protein kinases...
  38. Swarup S, Pradhan Sundd T, Verheyen E. Genome-wide identification of phospho-regulators of Wnt signaling in Drosophila. Development. 2015;142:1502-15 pubmed publisher
    ..As proof of principle, we established that Cdc37 and Gilgamesh/CK1γ inhibit and promote signaling, respectively, by functioning at analogous levels of these ..
  39. Rizzolo K, Kumar A, Kakihara Y, Phanse S, Minic Z, Snider J, et al. Systems analysis of the genetic interaction network of yeast molecular chaperones. Mol Omics. 2018;14:82-94 pubmed publisher
    ..Most notably, we observed Hsp10, Hsp70 Ssz1 chaperone, and Hsp90 cochaperone Cdc37 to be the main drivers of the network architecture...
  40. Mariño Enríquez A, Ou W, Cowley G, Luo B, Jonker A, Mayeda M, et al. Genome-wide functional screening identifies CDC37 as a crucial HSP90-cofactor for KIT oncogenic expression in gastrointestinal stromal tumors. Oncogene. 2014;33:1872-6 pubmed publisher
    ..proliferate for 5-7 weeks, at which point assessment of relative hairpin abundance identified the HSP90 cofactor, CDC37, as one of the top six GIST-specific essential genes...
  41. Ando M, Fiesel F, Hudec R, Caulfield T, Ogaki K, Górka Skoczylas P, et al. The PINK1 p.I368N mutation affects protein stability and ubiquitin kinase activity. Mol Neurodegener. 2017;12:32 pubmed publisher
    ..We found that binding of PINK1 p.I368N to the co-chaperone complex HSP90/CDC37 is reduced and stress-induced interaction with TOM40 of the mitochondrial protein import machinery is abolished...
  42. Kentala H, Koponen A, Vihinen H, Pirhonen J, Liebisch G, Pataj Z, et al. OSBP-related protein-2 (ORP2): a novel Akt effector that controls cellular energy metabolism. Cell Mol Life Sci. 2018;75:4041-4057 pubmed publisher
    ..ORP2 was found to form a physical complex with the key controllers of Akt activity, Cdc37, and Hsp90, and to co-localize with Cdc37 and active Akt(Ser473) at lamellipodial plasma membrane regions, in ..
  43. Eckl J, Rutz D, Haslbeck V, Zierer B, Reinstein J, Richter K. Cdc37 (cell division cycle 37) restricts Hsp90 (heat shock protein 90) motility by interaction with N-terminal and middle domain binding sites. J Biol Chem. 2013;288:16032-42 pubmed publisher
    The ATPase-driven dimeric molecular Hsp90 (heat shock protein 90) and its cofactor Cdc37 (cell division cycle 37 protein) are crucial to prevent the cellular depletion of many protein kinases...
  44. Wang L, Li L, Fu W, Jiang Z, You Q, Xu X. Optimization and bioevaluation of Cdc37-derived peptides: An insight into Hsp90-Cdc37 protein-protein interaction modulators. Bioorg Med Chem. 2017;25:233-240 pubmed publisher
    Targeting Hsp90-Cdc37 protein-protein interaction (PPI) is becoming an alternative approach for future anti-cancer drug development...
  45. Bunney T, Inglis A, Sanfelice D, Farrell B, Kerr C, Thompson G, et al. Disease Variants of FGFR3 Reveal Molecular Basis for the Recognition and Additional Roles for Cdc37 in Hsp90 Chaperone System. Structure. 2018;26:446-458.e8 pubmed publisher
    ..The Hsp90/Cdc37 chaperone system is essential for function of normal and neoplastic cells...
  46. Scholz G, Cartledge K, Hall N. Identification and characterization of Harc, a novel Hsp90-associating relative of Cdc37. J Biol Chem. 2001;276:30971-9 pubmed
    ..is known about the precise mechanisms by which the molecular chaperone Hsp90 recognizes its client proteins, Cdc37 has been shown to play a critical role in the targeting of Hsp90 to client protein kinases...
  47. Rao R, Nalluri S, Fiskus W, Balusu R, Joshi A, Mudunuru U, et al. Heat shock protein 90 inhibition depletes TrkA levels and signaling in human acute leukemia cells. Mol Cancer Ther. 2010;9:2232-42 pubmed publisher
    ..Treatment with 17-DMAG disrupted the binding of TrkA with hsp90 and the cochaperone cdc37, resulting in polyubiquitylation, proteasomal degradation, and depletion of TrkA...
  48. Jinwal U, Abisambra J, Zhang J, Dharia S, O Leary J, Patel T, et al. Cdc37/Hsp90 protein complex disruption triggers an autophagic clearance cascade for TDP-43 protein. J Biol Chem. 2012;287:24814-20 pubmed publisher
    ..Here, we show that part of the normal clearance cascade for TDP-43 involves the Cdc37/Hsp90 complex...
  49. Joo J, Dorsey F, Joshi A, Hennessy Walters K, Rose K, McCastlain K, et al. Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy. Mol Cell. 2011;43:572-85 pubmed publisher
    ..The Hsp90-Cdc37 chaperone complex coordinately regulates the activity of select kinases to orchestrate many facets of the stress ..
  50. Chou S, Patil R, Galstyan A, Gangalum P, Cavenee W, Furnari F, et al. Simultaneous blockade of interacting CK2 and EGFR pathways by tumor-targeting nanobioconjugates increases therapeutic efficacy against glioblastoma multiforme. J Control Release. 2016;244:14-23 pubmed publisher
    ..Downregulation of CK2 and EGFR also caused deactivation of heat shock protein 90 (Hsp90) co-chaperone Cdc37, which may suppress the activity of key cellular kinases...
  51. Chen X, Liu P, Wang Q, Li Y, Fu L, Fu H, et al. DCZ3112, a novel Hsp90 inhibitor, exerts potent antitumor activity against HER2-positive breast cancer through disruption of Hsp90-Cdc37 interaction. Cancer Lett. 2018;434:70-80 pubmed publisher
    ..DCZ3112 directly bound to the N-terminal domain of Hsp90 and inhibited Hsp90-Cdc37 interaction without inhibiting ATPase activity...
  52. Jakobs A, Himstedt F, Funk M, Korn B, Gaestel M, Niedenthal R. Ubc9 fusion-directed SUMOylation identifies constitutive and inducible SUMOylation. Nucleic Acids Res. 2007;35:e109 pubmed
    ..Of these, three were constitutively SUMOylated (FOS, CRSP9 and CDC37) while the remaining five substrates (CSNK2B, TAF10, HSF2BP, PSMC3 and DRG1) showed a stimulation-dependent ..
  53. Terasawa K, Minami Y. A client-binding site of Cdc37. FEBS J. 2005;272:4684-90 pubmed
    ..Among these, many specific protein kinases require the assistance of Hsp90 and its co-chaperone Cdc37/p50 for their biogenesis...
  54. Narayan M, Zhang J, Braswell K, Gibson C, Zitnyar A, Lee D, et al. Withaferin A Regulates LRRK2 Levels by Interfering with the Hsp90- Cdc37 Chaperone Complex. Curr Aging Sci. 2015;8:259-65 pubmed
    ..Previous work has shown that the chaperone heat shock protein 90 (Hsp90) and its co-chaperone Cdc37 interact with and stabilize LRRK2...
  55. Ota A, Zhang J, Ping P, Han J, Wang Y. Specific regulation of noncanonical p38alpha activation by Hsp90-Cdc37 chaperone complex in cardiomyocyte. Circ Res. 2010;106:1404-12 pubmed publisher
    ..Using both proteomic and biochemical tools, we established that heat shock protein (Hsp)90-Cdc37 chaperones are part of the p38alpha signaling complex in mammalian cells both in vitro and in vivo...
  56. De Nardo D, Masendycz P, Ho S, Cross M, Fleetwood A, Reynolds E, et al. A central role for the Hsp90.Cdc37 molecular chaperone module in interleukin-1 receptor-associated-kinase-dependent signaling by toll-like receptors. J Biol Chem. 2005;280:9813-22 pubmed
    ..mass spectrometric-based approach, we have identified a cohort of chaperones and co-chaperones including Hsp90 and Cdc37, which bind to IRAK-1 but not IRAK-4 in 293T cells...
  57. Li D, Xu T, Cao Y, Wang H, Li L, Chen S, et al. A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for RIP3 activation during necroptosis. Proc Natl Acad Sci U S A. 2015;112:5017-22 pubmed publisher
    ..We report here that RIP3 activation following the induction of necroptosis requires the activity of an HSP90 and CDC37 cochaperone complex. This complex physically associates with RIP3...
  58. Xu Y, Liu F, Liu J, Wang D, Yan Y, Ji S, et al. The co-chaperone Cdc37 regulates the rabies virus phosphoprotein stability by targeting to Hsp90AA1 machinery. Sci Rep. 2016;6:27123 pubmed publisher
    b>Cdc37, as a kinase-specific co-chaperone of the chaperone Hsp90AA1 (Hsp90), actively aids with the maturation, stabilization and activation of the cellular or viral kinase/kinase-like targets...
  59. Woodford M, Dunn D, Blanden A, Capriotti D, Loiselle D, Prodromou C, et al. The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding. Nat Commun. 2016;7:12037 pubmed publisher
    ..Our findings suggest that FNIPs expression can potentially serve as a predictive indicator of tumour response to Hsp90 inhibitors. ..
  60. Dushukyan N, Dunn D, Sager R, Woodford M, Loiselle D, Daneshvar M, et al. Phosphorylation and Ubiquitination Regulate Protein Phosphatase 5 Activity and Its Prosurvival Role in Kidney Cancer. Cell Rep. 2017;21:1883-1895 pubmed publisher
    ..Overexpression of the phosphomimetic T362E-PP5 mutant hyper-dephosphorylates substrates such as the co-chaperone Cdc37 and glucocorticoid receptor in cells...
  61. Smith J, de Billy E, Hobbs S, Powers M, Prodromou C, Pearl L, et al. Restricting direct interaction of CDC37 with HSP90 does not compromise chaperoning of client proteins. Oncogene. 2015;34:15-26 pubmed publisher
    ..Kinases are a substantial and important subset of clients requiring the key cochaperone CDC37. We sought an improved understanding of protein kinase chaperoning by CDC37 in cancer cells...
  62. Li D, Li C, Li L, Chen S, Wang L, Li Q, et al. Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3-dependent Necroptosis. Cell Chem Biol. 2016;23:257-266 pubmed publisher
    ..a previously uncharacterized cysteine 420 in the middle domain of HSP90 and dissociates HSP90 from its cochaperone CDC37, which leads to inhibition of RIP3-dependent necroptosis and promotion of apoptosis in multiple cancer cell lines...
  63. Jin L, Huang R, Huang X, Zhang B, Ji M, Wang H. Discovery of 18?-glycyrrhetinic acid conjugated aminobenzothiazole derivatives as Hsp90-Cdc37 interaction disruptors that inhibit cell migration and reverse drug resistance. Bioorg Med Chem. 2018;26:1759-1775 pubmed publisher
    ..aminobenzothiazole derivatives were designed, synthesized and evaluated for disruption activity of Hsp90-Cdc37 as well as the effects of in vitro cell migration...
  64. Yun C, Boggon T, Li Y, Woo M, Greulich H, Meyerson M, et al. Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell. 2007;11:217-27 pubmed
    ..Strikingly, direct binding measurements show that gefitinib binds 20-fold more tightly to the L858R mutant than to the wild-type enzyme. ..
  65. Radulovic M, Crane E, Crawford M, Godovac Zimmermann J, Yu V. CKS proteins protect mitochondrial genome integrity by interacting with mitochondrial single-stranded DNA-binding protein. Mol Cell Proteomics. 2010;9:145-52 pubmed publisher
    ..These features are consistent with the hypothesis of CKS-dependent regulation of mtSSB function and support a direct role of cell cycle proteins in controlling mitochondrial DNA replication. ..
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    ..The effects of gedunin on expression of heat shock protein 90 (HSP90), its cochaperone Cdc37, and HSP client proteins (AKT, ErbB2, and HSF1) were evaluated by real-time PCR...
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    ..Here, we show that the heteromeric complex containing the molecular chaperones Hsp90 and Cdc37/p50 interacts with the kinase domain of LKB1...
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    ..The cell division cycle 37 homolog (Cdc37), a protein kinase-specific co-chaperone for Hsp90, was identified as a Vav3 interacting ..
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    ..These domains are tetratricopeptide repeat (or TPR), apolipophorin III (or apoLp-III) and Hsp90 co-chaperone Cdc37. Subsequent analysis divided USPA-like domains based on the ability to bind ATP...
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    ..90 ± 1.45)% and (35.60 ± 3.55)% (P=0.001) in the HL60/Bcr-Abl cell line groups. FW-04-806 dissociated Hsp90/Cdc37 chaperon/co-chaperon complex, followed by degradation of the Hsp90 proteins through proteasome pathway without ..
  71. Czemeres J, Buse K, Verkhivker G. Atomistic simulations and network-based modeling of the Hsp90-Cdc37 chaperone binding with Cdk4 client protein: A mechanism of chaperoning kinase clients by exploiting weak spots of intrinsically dynamic kinase domains. PLoS ONE. 2017;12:e0190267 pubmed publisher
    A fundamental role of the Hsp90 and Cdc37 chaperones in mediating conformational development and activation of diverse protein kinase clients is essential in signal transduction...
  72. Imai Y, Kanao T, Sawada T, Kobayashi Y, Moriwaki Y, Ishida Y, et al. The loss of PGAM5 suppresses the mitochondrial degeneration caused by inactivation of PINK1 in Drosophila. PLoS Genet. 2010;6:e1001229 pubmed publisher
    ..These results suggest that PGAM5 negatively regulates the PINK1 pathway related to maintenance of the mitochondria and, furthermore, that PGAM5 acts between PINK1 and Parkin, or functions independently of Parkin downstream of PINK1. ..
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    ..Only WGA-TA degraded HSP90-Cdc37 complexing by 60-70% versus controls...
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    ..AUY922, whereas reactivation of Akt was related to the activity of the HSP90 co-chaperone, cell division cycle 37 (CDC37), in that knockdown of CDC37 inhibited Akt reactivation in mutant colon cancer cells treated with AUY922...
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    ..PP5-mediated dephosphorylation of the cochaperone Cdc37 is essential for activation of Hsp90-dependent kinases. However, the details of this mechanism remain unknown...
  76. Jiang F, Wang H, Bao Q, Wang L, Jin Y, Zhang Q, et al. Optimization and biological evaluation of celastrol derivatives as Hsp90-Cdc37 interaction disruptors with improved druglike properties. Bioorg Med Chem. 2016;24:5431-5439 pubmed publisher
    ..The Hsp90 multichaperone complex has important roles in the growth and/or survival of cancer cells. Cdc37, as a cochaperone, associates kinase clients to Hsp90 and promotes the development of malignant tumors...
  77. Huang W, Ye M, Zhang L, Wu Q, Zhang M, Xu J, et al. FW-04-806 inhibits proliferation and induces apoptosis in human breast cancer cells by binding to N-terminus of Hsp90 and disrupting Hsp90-Cdc37 complex formation. Mol Cancer. 2014;13:150 pubmed publisher
    ..to the N-terminal domain of Hsp90 and found that FW-04-806 inhibits Hsp90/cell division cycle protein 37 (Cdc37) chaperone/co-chaperone interactions, but does not affect ATP-binding capability of Hsp90, thereby leading to the ..
  78. Abbas Terki T, Briand P, Donze O, Picard D. The Hsp90 co-chaperones Cdc37 and Sti1 interact physically and genetically. Biol Chem. 2002;383:1335-42 pubmed
    b>Cdc37 associates with the heat-shock protein 90 (Hsp90) molecular chaperone as one of several auxiliary proteins that are collectively referred to as Hsp90 co-chaperones...
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    ..Notably, the immature ErbB2 point mutant remains sensitive to GA, suggesting that mature and nascent client kinases may use distinct motifs to interact with the Hsp90 chaperone complex. ..
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    ..of TAK1 as a client protein of the 90 kDa heat-shock protein (Hsp90)/cell division cycle protein 37 (Cdc37) chaperones...
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    b>Cdc37 is a molecular chaperone closely associated with the folding of protein kinases. Results from studies using a yeast model system showed that it was also important for activation of the human androgen receptor (AR)...
  82. Gloeckner C, Kinkl N, Schumacher A, Braun R, O Neill E, Meitinger T, et al. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum Mol Genet. 2006;15:223-32 pubmed
    ..This suggests that the pathology of PD caused by the I2020T mutation is associated with an increase rather than a loss in LRRK2 kinase activity. ..
  83. Kise Y, Takenaka K, Tezuka T, Yamamoto T, Miki H. Fused kinase is stabilized by Cdc37/Hsp90 and enhances Gli protein levels. Biochem Biophys Res Commun. 2006;351:78-84 pubmed
    ..have investigated proteins co-precipitated with mammalian Fu and identified a kinase-specific chaperone complex, Cdc37/Hsp90, as a novel-binding partner of Fu...
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    ..studies reveal that conventional and novel, but not atypical, PKC isozymes bind the chaperones Hsp90 and Cdc37 through a PXXP-dependent mechanism...
  85. Azoitei N, Hoffmann C, Ellegast J, Ball C, Obermayer K, Gößele U, et al. Targeting of KRAS mutant tumors by HSP90 inhibitors involves degradation of STK33. J Exp Med. 2012;209:697-711 pubmed publisher
    ..Here, using a mass spectrometry-based screen for STK33 protein interaction partners, we report that the HSP90/CDC37 chaperone complex binds to and stabilizes STK33 in human cancer cells...
  86. Wang Y, Xu W, Zhou D, Neckers L, Chen S. Coordinated regulation of serum- and glucocorticoid-inducible kinase 3 by a C-terminal hydrophobic motif and Hsp90-Cdc37 chaperone complex. J Biol Chem. 2014;289:4815-26 pubmed publisher
    ..Here we report that SGK3 stability and kinase activation are regulated by the Hsp90-Cdc37 chaperone complex...
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  88. Kim H, Abd Elmageed Z, Davis C, El Bahrawy A, Naura A, Ekaidi I, et al. Correlation between PDZK1, Cdc37, Akt and breast cancer malignancy: the role of PDZK1 in cell growth through Akt stabilization by increasing and interacting with Cdc37. Mol Med. 2014;20:270-9 pubmed publisher
    ..sensitive to heat shock protein 90 (HSP90) inhibition, increased levels of the cochaperone cell division cycle 37 (Cdc37), as well as its ability to bind PDZK1, appear to play a larger role in kinase stability...
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    Selective recruitment of protein kinases to the Hsp90 system is mediated by the adaptor co-chaperone Cdc37. We show that assembly of CDK4 and CDK6 into protein complexes is differentially regulated by the Cdc37-Hsp90 system...
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    Cell division cycle 37 (Cdc37) is an important partner for heat shock protein 90 (HSP90), assisting in molecular chaperone activities, particularly with regard to the regulation of protein kinases...
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    ..LKB1 from cells and establish that it is associated with the heat-shock protein 90 (Hsp90) chaperone and the Cdc37 kinase-specific targetting subunit for Hsp90...