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Concept
CDC42
Résumé
Cell division control protein 42 homolog (Cdc42 or CDC42) is a protein that in humans is encoded by the CDC42 gene. Cdc42 is involved in regulation of the cell cycle. It was originally identified in S. cerevisiae (yeast) as a mediator of cell division, and is now known to influence a variety of signaling events and cellular processes in a variety of organisms from yeast to mammals.
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 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.
Cdc42 is a homodimer with A and B chains. Its total length is 191 amino acids and its theoretical weight is 21.33 kDa. Its sequence domains include a P-loop containing nucleoside triphosphate hydrolase and a small GTP-binding protein domain.
Cdc42 cycles between an active GTP-bound state and an inactive GDP-bound state. This process is regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase.
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.
Source officielle
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