CDC42

Human Cdc42 is a small GTPase of the Rho family, which regulates signaling pathways that control diverse cellular functions including cell morphology, cell migration, endocytosis, cell polarity and cell cycle progression. Rho GTPases are central to dynamic actin cytoskeletal assembly and rearrangement that are the basis of cell-cell adhesion and migration. Activated Cdc42 activates by causing conformational changes in p21-activated kinases PAK1 and PAK2, which in turn initiate actin reorganization and regulate cell adhesion, migration, and invasion. == Structure ==

Cdc42 is a homodimer with A and B chains. Its total length is 191 amino acids and its theoretical weight is 21.33 kDa. == Role in cancer ==

Recently, Cdc42 has been shown to actively assist in cancer progression. Several studies have established the basis for this and hypothesized about the underlying mechanisms. Cdc42 is overexpressed in non-small cell lung cancer, colorectal adenocarcinoma, melanoma, breast cancer, and testicular cancer. Elevated levels of the protein have been correlated with negative patient survival. Cdc42 has also been shown to be required for both G1-S phase progression and mitosis, and it also modulates the transcription factors SRF, STAT3, and NFkB. Cdc42 expression was gradually increased showing significant difference and was significantly higher in HeLa cells than in regular cells. The migration ability of HeLa cells transfected with Cdc42 was higher than that of non-transfected cells. Levels of β1 integrin were reduced in Cdc42-deficient cells. β1 integrin is important for adhesion to the extracellular matrix, and could be important for the initial attachment to endothelial cells as well. Knocking down β1 integrin inhibited cancer cell migration, whereas overexpressing the integrin in Cdc42-deficient cells restored endothelial invasion. There was evidence that Cdc42 inhibition by AZA197 treatment suppresses proliferative and pro-survival signaling pathways via PAK1-ERK signaling and reduces colon cancer cell migration and invasion. In mice, systemic AZA197 treatment in vivo reduced primary tumor growth and prolonged survival. Therapy targeting Rho GTPase Cdc42 signaling pathways may be effective for treatment of patients with advanced colon cancer overexpressing Cdc42, and particularly those with KRAS-mutant disease. == Takenouchi-Kosaki syndrome ==

Mutations in the CDC42 gene are responsible for the Takenouchi-Kosaki syndrome, an autosomal-dominant complex congenital developmental disorder associated with thrombocytopenia. Alleic variants that are associated with the syndrome include mutations in the CDC42 gene that are expressed at the protein level as Ile21Thr, Tyr64Cys, Arg66Gly, Cys81Phe, Ser83Pro, or Glu171Lys. == Interactions ==

CDC42 has been shown to interact with: • ARHGAP1, • ARHGDIA, • BAIAP2, • BNIP2, • BNIPL, • CDC42EP2, • CDC42EP3, • ERRFI1, • GDI1, • IQGAP1, • IQGAP2, • ITSN1, • MAP3K10, • PAK1, • PAK2, • PAK4. • PARD6A, • PARD6B, • Phospholipase D1, • RICS • TRIP10, • WASL, • Wiskott–Aldrich syndrome protein, ==See also==