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Gene Review

Cdc42  -  cell division cycle 42

Mus musculus

Synonyms: AI747189, AU018915, Cell division control protein 42 homolog, G25K GTP-binding protein
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Disease relevance of Cdc42


High impact information on Cdc42

  • Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells [6].
  • Here, we show that activation of Cdc42 protects the EGF receptor from the negative regulatory activity of the c-Cbl ubiquitin ligase [7].
  • Cdc42 is a Ras-related protein that has been implicated in the control of normal cell growth, and when improperly regulated, in cellular transformation and invasiveness [7].
  • Activated Cdc42 sequesters c-Cbl and prevents EGF receptor degradation [7].
  • Activation requires an intact effector domain and isoprenylation of Cdc42 and Rac1 [8].

Chemical compound and disease context of Cdc42

  • GDP/GTP exchange assay data and studies with pertussis (PTX) toxin suggest that mastoparan may work directly to activate Cdc42 and not via PTX-sensitive heterotrimeric GTP-binding proteins [9].

Biological context of Cdc42


Anatomical context of Cdc42

  • Mechanistic studies indicate that p53 prevents the initiating steps of filopodia formation downstream of Cdc42 [10].
  • The p21-activated kinases (PAKs) are direct targets of active Rac and Cdc42 which can induce the assembly of polarized cytoskeletal structures when expressed in fibroblasts, suggesting that they may play a role in mediating the effects of these GTPases on cytoskeletal dynamics [14].
  • Activation of Rac-1, Rac-2, and Cdc42 by hemopoietic growth factors or cross-linking of the B-lymphocyte receptor for antigen [15].
  • Here we have examined the hematopoietic properties and the hematopoietic stem/progenitor cell (HSP) functions of gene-targeted mice carrying null alleles of cdc42gap, a negative regulator of Cdc42 [13].
  • The process of macropinocytosis is an essential aspect of normal cell function, contributing to both growth and motile processes of cells. p21-activated kinases (PAKs) are targets for activated Rac and Cdc42 guanosine 5'-triphosphatases and have been shown to regulate the actin-myosin cytoskeleton [16].

Associations of Cdc42 with chemical compounds


Physical interactions of Cdc42

  • CAPRI interacted constitutively with both Cdc42 and Rac1 and translocated to phagocytic cups during FcgammaR-mediated phagocytosis [22].
  • The Rho subfamily GTP-binding protein Cdc42 mediates actin cytoskeletal rearrangements and cell cycle progression and is essential for Ras transformation [23].
  • This inhibitory mechanism seems to act through steric hindrance of Cdc42 binding by an intramolecular interaction between the intersectin 1L SH3 domain region and the adjacent DH domain [24].
  • Residue His556 of this region, in particular, is important for this activity, since the H556A mutant retained the GEF catalytic capability and the binding activity toward Cdc42 and RhoA in vitro but was deficient in oligomer formation [25].
  • By fluorescent resonance energy transfer (FRET) analysis, we demonstrate that this motif is required for Cdc42 binding and Drf3 recruitment to the leading edge and, surprisingly, to the microtubule organizing center (MTOC) of migrating fibroblasts [26].

Regulatory relationships of Cdc42


Other interactions of Cdc42

  • The mechanisms through which the small GTPases Rac1 and Cdc42 regulate the formation of membrane ruffles, lamellipodia, and filopodia are currently unknown [14].
  • The small G proteins Cdc42, Rac1, and Rac2 regulate the rearrangements of actin and membrane necessary for Fcgamma receptor-mediated phagocytosis by macrophages [31].
  • Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASP [1].
  • Interestingly, p53 exerted a selective effect on Cdc42-mediated cell functions [10].
  • Previous studies have dissociated actin cytoskeletal activity from the transforming potential of RhoA and Cdc42 [32].

Analytical, diagnostic and therapeutic context of Cdc42


  1. Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASP. Labno, C.M., Lewis, C.M., You, D., Leung, D.W., Takesono, A., Kamberos, N., Seth, A., Finkelstein, L.D., Rosen, M.K., Schwartzberg, P.L., Burkhardt, J.K. Curr. Biol. (2003) [Pubmed]
  2. Activation of clg, a novel dbl family guanine nucleotide exchange factor gene, by proviral insertion at evi24, a common integration site in B cell and myeloid leukemias. Himmel, K.L., Bi, F., Shen, H., Jenkins, N.A., Copeland, N.G., Zheng, Y., Largaespada, D.A. J. Biol. Chem. (2002) [Pubmed]
  3. Rac1/Cdc42 and RhoA GTPases antagonistically regulate chondrocyte proliferation, hypertrophy, and apoptosis. Wang, G., Beier, F. J. Bone Miner. Res. (2005) [Pubmed]
  4. Rac1 and Cdc42 but not RhoA or Rho kinase activities are required for neurite outgrowth induced by the Netrin-1 receptor DCC (deleted in colorectal cancer) in N1E-115 neuroblastoma cells. Li, X., Saint-Cyr-Proulx, E., Aktories, K., Lamarche-Vane, N. J. Biol. Chem. (2002) [Pubmed]
  5. Rac1 and Cdc42 are required for phagocytosis, but not NF-kappaB-dependent gene expression, in macrophages challenged with Pseudomonas aeruginosa. Lee, D.J., Cox, D., Li, J., Greenberg, S. J. Biol. Chem. (2000) [Pubmed]
  6. Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Gomes, E.R., Jani, S., Gundersen, G.G. Cell (2005) [Pubmed]
  7. Activated Cdc42 sequesters c-Cbl and prevents EGF receptor degradation. Wu, W.J., Tu, S., Cerione, R.A. Cell (2003) [Pubmed]
  8. The 70 kDa S6 kinase complexes with and is activated by the Rho family G proteins Cdc42 and Rac1. Chou, M.M., Blenis, J. Cell (1996) [Pubmed]
  9. A link between Cdc42 and syntaxin is involved in mastoparan-stimulated insulin release. Daniel, S., Noda, M., Cerione, R.A., Sharp, G.W. Biochemistry (2002) [Pubmed]
  10. Regulation of Cdc42-mediated morphological effects: a novel function for p53. Gadéa, G., Lapasset, L., Gauthier-Rouvière, C., Roux, P. EMBO J. (2002) [Pubmed]
  11. A role for Cdc42 in macrophage chemotaxis. Allen, W.E., Zicha, D., Ridley, A.J., Jones, G.E. J. Cell Biol. (1998) [Pubmed]
  12. Regulated membrane localization of Tiam1, mediated by the NH2-terminal pleckstrin homology domain, is required for Rac-dependent membrane ruffling and C-Jun NH2-terminal kinase activation. Michiels, F., Stam, J.C., Hordijk, P.L., van der Kammen, R.A., Ruuls-Van Stalle, L., Feltkamp, C.A., Collard, J.G. J. Cell Biol. (1997) [Pubmed]
  13. Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftment. Wang, L., Yang, L., Filippi, M.D., Williams, D.A., Zheng, Y. Blood (2006) [Pubmed]
  14. Localization of p21-activated kinase 1 (PAK1) to pinocytic vesicles and cortical actin structures in stimulated cells. Dharmawardhane, S., Sanders, L.C., Martin, S.S., Daniels, R.H., Bokoch, G.M. J. Cell Biol. (1997) [Pubmed]
  15. Activation of Rac-1, Rac-2, and Cdc42 by hemopoietic growth factors or cross-linking of the B-lymphocyte receptor for antigen. Grill, B., Schrader, J.W. Blood (2002) [Pubmed]
  16. Regulation of macropinocytosis by p21-activated kinase-1. Dharmawardhane, S., Schürmann, A., Sells, M.A., Chernoff, J., Schmid, S.L., Bokoch, G.M. Mol. Biol. Cell (2000) [Pubmed]
  17. A Rac/Cdc42-specific exchange factor, GEFT, induces cell proliferation, transformation, and migration. Guo, X., Stafford, L.J., Bryan, B., Xia, C., Ma, W., Wu, X., Liu, D., Songyang, Z., Liu, M. J. Biol. Chem. (2003) [Pubmed]
  18. Epidermal growth factor-dependent regulation of Cdc42 is mediated by the Src tyrosine kinase. Tu, S., Wu, W.J., Wang, J., Cerione, R.A. J. Biol. Chem. (2003) [Pubmed]
  19. Gene Targeting of Cdc42 and Cdc42GAP Affirms the Critical Involvement of Cdc42 in Filopodia Induction, Directed Migration, and Proliferation in Primary Mouse Embryonic Fibroblasts. Yang, L., Wang, L., Zheng, Y. Mol. Biol. Cell (2006) [Pubmed]
  20. ROCK and nuclear factor-kappaB-dependent activation of cyclooxygenase-2 by Rho GTPases: effects on tumor growth and therapeutic consequences. Benitah, S.A., Valerón, P.F., Lacal, J.C. Mol. Biol. Cell (2003) [Pubmed]
  21. Targeted disruption of the gene for the PAK5 kinase in mice. Li, X., Minden, A. Mol. Cell. Biol. (2003) [Pubmed]
  22. An essential function for the calcium-promoted Ras inactivator in Fcgamma receptor-mediated phagocytosis. Zhang, J., Guo, J., Dzhagalov, I., He, Y.W. Nat. Immunol. (2005) [Pubmed]
  23. Transformation activity of Cdc42 requires a region unique to Rho-related proteins. Wu, W.J., Lin, R., Cerione, R.A., Manor, D. J. Biol. Chem. (1998) [Pubmed]
  24. Intersectin 1L guanine nucleotide exchange activity is regulated by adjacent src homology 3 domains that are also involved in endocytosis. Zamanian, J.L., Kelly, R.B. Mol. Biol. Cell (2003) [Pubmed]
  25. Oligomerization of DH domain is essential for Dbl-induced transformation. Zhu, K., Debreceni, B., Bi, F., Zheng, Y. Mol. Cell. Biol. (2001) [Pubmed]
  26. Disruption of the Diaphanous-related formin Drf1 gene encoding mDia1 reveals a role for Drf3 as an effector for Cdc42. Peng, J., Wallar, B.J., Flanders, A., Swiatek, P.J., Alberts, A.S. Curr. Biol. (2003) [Pubmed]
  27. Cdc42 and Rac small G proteins activated by trans-interactions of nectins are involved in activation of c-Jun N-terminal kinase, but not in association of nectins and cadherin to form adherens junctions, in fibroblasts. Honda, T., Shimizu, K., Kawakatsu, T., Fukuhara, A., Irie, K., Nakamura, T., Matsuda, M., Takai, Y. Genes Cells (2003) [Pubmed]
  28. Regulation of gene expression by the small GTPase Rho through the ERK6 (p38 gamma) MAP kinase pathway. Marinissen, M.J., Chiariello, M., Gutkind, J.S. Genes Dev. (2001) [Pubmed]
  29. Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin. Wu, X., Quondamatteo, F., Lefever, T., Czuchra, A., Meyer, H., Chrostek, A., Paus, R., Langbein, L., Brakebusch, C. Genes Dev. (2006) [Pubmed]
  30. Rac downregulates Rho activity: reciprocal balance between both GTPases determines cellular morphology and migratory behavior. Sander, E.E., ten Klooster, J.P., van Delft, S., van der Kammen, R.A., Collard, J.G. J. Cell Biol. (1999) [Pubmed]
  31. Cdc42, Rac1, and Rac2 display distinct patterns of activation during phagocytosis. Hoppe, A.D., Swanson, J.A. Mol. Biol. Cell (2004) [Pubmed]
  32. Dependence of Dbl and Dbs transformation on MEK and NF-kappaB activation. Whitehead, I.P., Lambert, Q.T., Glaven, J.A., Abe, K., Rossman, K.L., Mahon, G.M., Trzaskos, J.M., Kay, R., Campbell, S.L., Der, C.J. Mol. Cell. Biol. (1999) [Pubmed]
  33. WIP regulates N-WASP-mediated actin polymerization and filopodium formation. Martinez-Quiles, N., Rohatgi, R., Antón, I.M., Medina, M., Saville, S.P., Miki, H., Yamaguchi, H., Takenawa, T., Hartwig, J.H., Geha, R.S., Ramesh, N. Nat. Cell Biol. (2001) [Pubmed]
  34. Identification of H-Ras, RhoA, Rac1 and Cdc42 responsive genes. Teramoto, H., Malek, R.L., Behbahani, B., Castellone, M.D., Lee, N.H., Gutkind, J.S. Oncogene (2003) [Pubmed]
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