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Protein-coding gene in the species Homo sapiens
Hsp90 co-chaperone Cdc37 is a protein that in humans is encoded by the CDC37 gene .[ 5] This protein is highly similar to Cdc 37, a cell division cycle control protein of Saccharomyces cerevisiae . This protein is a HSP90 Co-chaperone [ 6] with specific function in cell signal transduction . It has been shown to form complex with Hsp90 and a variety of protein kinases including CDK4 , CDK6 , SRC , RAF1 , MOK , as well as eIF-2 alpha kinases. It is thought to play a critical role in directing Hsp90 to its target kinases.[ 7]
CDC37 has been shown to interact with:
Domain architecture [ edit ]
CDC37 consists of three structural domains . The N-terminal domain binds to protein kinases .[ 16] The central domain is the Hsp90 chaperone (heat shock protein 90) binding domain.[ 17] The function of the C-terminal domain is unclear.
^ a b c GRCh38: Ensembl release 89: ENSG00000105401 – Ensembl , May 2017
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000019471 – Ensembl , May 2017
^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ a b Dai K, Kobayashi R, Beach D (September 1996). "Physical interaction of mammalian CDC37 with CDK4" . The Journal of Biological Chemistry . 271 (36): 22030–22034. doi :10.1074/jbc.271.36.22030 . PMID 8703009 .
^ Mollapour M, Neckers L (March 2012). "Post-translational modifications of Hsp90 and their contributions to chaperone regulation" . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1823 (3): 648–655. doi :10.1016/j.bbamcr.2011.07.018 . PMC 3226900 . PMID 21856339 .
^ "Entrez Gene: CDC37 cell division cycle 37 homolog (S. cerevisiae)" .
^ Stepanova L, Leng X, Parker SB, Harper JW (June 1996). "Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4" . Genes & Development . 10 (12): 1491–1502. doi :10.1101/gad.10.12.1491 . PMID 8666233 .
^ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry" . Molecular Systems Biology . 3 (1): 89. doi :10.1038/msb4100134 . PMC 1847948 . PMID 17353931 .
^ Lamphere L, Fiore F, Xu X, Brizuela L, Keezer S, Sardet C, et al. (April 1997). "Interaction between Cdc37 and Cdk4 in human cells" . Oncogene . 14 (16): 1999–2004. doi :10.1038/sj.onc.1201036 . PMID 9150368 .
^ Roe SM, Ali MM, Meyer P, Vaughan CK, Panaretou B, Piper PW, et al. (January 2004). "The Mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(cdc37)" . Cell . 116 (1): 87–98. doi :10.1016/S0092-8674(03)01027-4 . PMID 14718169 . S2CID 797232 .
^ Silverstein AM, Grammatikakis N, Cochran BH, Chinkers M, Pratt WB (August 1998). "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" . The Journal of Biological Chemistry . 273 (32): 20090–20095. doi :10.1074/jbc.273.32.20090 . PMID 9685350 .
^ Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology . 6 (2): 97–105. doi :10.1038/ncb1086 . PMID 14743216 . S2CID 11683986 .
^ a b Chen G, Cao P, Goeddel DV (February 2002). "TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90" . Molecular Cell . 9 (2): 401–410. doi :10.1016/S1097-2765(02)00450-1 . PMID 11864612 .
^ Boudeau J, Deak M, Lawlor MA, Morrice NA, Alessi DR (March 2003). "Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability" . The Biochemical Journal . 370 (Pt 3): 849–857. doi :10.1042/BJ20021813 . PMC 1223241 . PMID 12489981 .
^ Kimura Y, Rutherford SL, Miyata Y, Yahara I, Freeman BC, Yue L, et al. (July 1997). "Cdc37 is a molecular chaperone with specific functions in signal transduction" . Genes & Development . 11 (14): 1775–1785. doi :10.1101/gad.11.14.1775 . PMID 9242486 .
^ Turnbull EL, Martin IV, Fantes PA (August 2005). "Cdc37 maintains cellular viability in Schizosaccharomyces pombe independently of interactions with heat-shock protein 90" . The FEBS Journal . 272 (16): 4129–4140. doi :10.1111/j.1742-4658.2005.04825.x . PMID 16098195 . S2CID 23442218 .
Dey B, Lightbody JJ, Boschelli F (September 1996). "CDC37 is required for p60v-src activity in yeast" . Molecular Biology of the Cell . 7 (9): 1405–1417. doi :10.1091/mbc.7.9.1405 . PMC 275990 . PMID 8885235 .
Lamphere L, Fiore F, Xu X, Brizuela L, Keezer S, Sardet C, et al. (April 1997). "Interaction between Cdc37 and Cdk4 in human cells" . Oncogene . 14 (16): 1999–2004. doi :10.1038/sj.onc.1201036 . PMID 9150368 .
Kimura Y, Rutherford SL, Miyata Y, Yahara I, Freeman BC, Yue L, et al. (July 1997). "Cdc37 is a molecular chaperone with specific functions in signal transduction" . Genes & Development . 11 (14): 1775–1785. doi :10.1101/gad.11.14.1775 . PMID 9242486 .
Silverstein AM, Grammatikakis N, Cochran BH, Chinkers M, Pratt WB (August 1998). "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" . The Journal of Biological Chemistry . 273 (32): 20090–20095. doi :10.1074/jbc.273.32.20090 . PMID 9685350 .
Grammatikakis N, Lin JH, Grammatikakis A, Tsichlis PN, Cochran BH (March 1999). "p50(cdc37) acting in concert with Hsp90 is required for Raf-1 function" . Molecular and Cellular Biology . 19 (3): 1661–1672. doi :10.1128/mcb.19.3.1661 . PMC 83960 . PMID 10022854 .
O'Keeffe B, Fong Y, Chen D, Zhou S, Zhou Q (January 2000). "Requirement for a kinase-specific chaperone pathway in the production of a Cdk9/cyclin T1 heterodimer responsible for P-TEFb-mediated tat stimulation of HIV-1 transcription" . The Journal of Biological Chemistry . 275 (1): 279–287. doi :10.1074/jbc.275.1.279 . PMID 10617616 .
Hartson SD, Irwin AD, Shao J, Scroggins BT, Volk L, Huang W, Matts RL (June 2000). "p50(cdc37) is a nonexclusive Hsp90 cohort which participates intimately in Hsp90-mediated folding of immature kinase molecules". Biochemistry . 39 (25): 7631–7644. doi :10.1021/bi000315r . PMID 10858314 .
Shao J, Grammatikakis N, Scroggins BT, Uma S, Huang W, Chen JJ, et al. (January 2001). "Hsp90 regulates p50(cdc37) function during the biogenesis of the activeconformation of the heme-regulated eIF2 alpha kinase" . The Journal of Biological Chemistry . 276 (1): 206–214. doi :10.1074/jbc.M007583200 . PMID 11036079 .
Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination" . Genome Research . 10 (11): 1788–1795. doi :10.1101/gr.143000 . PMC 310948 . PMID 11076863 .
Rao J, Lee P, Benzeno S, Cardozo C, Albertus J, Robins DM, Caplan AJ (February 2001). "Functional interaction of human Cdc37 with the androgen receptor but not with the glucocorticoid receptor" . The Journal of Biological Chemistry . 276 (8): 5814–5820. doi :10.1074/jbc.M007385200 . PMID 11085988 .
Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (September 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing" . EMBO Reports . 1 (3): 287–292. doi :10.1093/embo-reports/kvd058 . PMC 1083732 . PMID 11256614 .
Scholz GM, Cartledge K, Hall NE (August 2001). "Identification and characterization of Harc, a novel Hsp90-associating relative of Cdc37" . The Journal of Biological Chemistry . 276 (33): 30971–30979. doi :10.1074/jbc.M103889200 . PMID 11413142 .
Chen G, Cao P, Goeddel DV (February 2002). "TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90" . Molecular Cell . 9 (2): 401–410. doi :10.1016/S1097-2765(02)00450-1 . PMID 11864612 .
Siligardi G, Panaretou B, Meyer P, Singh S, Woolfson DN, Piper PW, et al. (June 2002). "Regulation of Hsp90 ATPase activity by the co-chaperone Cdc37p/p50cdc37" . The Journal of Biological Chemistry . 277 (23): 20151–20159. doi :10.1074/jbc.M201287200 . PMID 11916974 .
Basso AD, Solit DB, Chiosis G, Giri B, Tsichlis P, Rosen N (October 2002). "Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function" . The Journal of Biological Chemistry . 277 (42): 39858–39866. doi :10.1074/jbc.M206322200 . PMID 12176997 .
Abbas-Terki T, Briand PA, Donzé O, Picard D (September 2002). "The Hsp90 co-chaperones Cdc37 and Sti1 interact physically and genetically". Biological Chemistry . 383 (9): 1335–1342. doi :10.1515/BC.2002.152 . PMID 12437126 . S2CID 9277739 .
Boudeau J, Deak M, Lawlor MA, Morrice NA, Alessi DR (March 2003). "Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability" . The Biochemical Journal . 370 (Pt 3): 849–857. doi :10.1042/BJ20021813 . PMC 1223241 . PMID 12489981 .