1. CDC42 a low molecular weight GTP-binding protein originally designated G(p) and also called G25K Chromosomal location: 1p36.1 The CDC42 protein binds to either GDP or GTP (Guanine DiPhosphate or Guanine TriPhosphate). There are many mechanisms that regulate when the CDC42 protein is to be activated. When CDC42 is inactive, it is bound to GDP. However, when it is activated, it binds GTP instead. CELL DIVISION CYCLE 42

2. CDC4 Gene Ensembl Gene Report Stable ID: ENST00000315545 Exons: 6 Transcript length: 2106 bp Translation length: 191 residues Link http://www.ensembl.org/Homo_sapiens/geneview?gene=ENSG00000070831

3. Rittinger, K. et al. (1997). Nature, This is the crystalized structure of Cdc42 bound to a non- hydrolyzable GTP analog

5. Function Rho-family guanosine triphosphatases (GTPases) such as Rho, Cdc42, and Rac, act as molecular switches in signal transduction pathways that lead to the organization of the actin cytoskeleton as well as transcription of a genes leading to progression of the cell cycle (G1 to S phase of cell life cycle). coordinated regulation of actin filament assembly and disassembly and of MAP kinase pathways by Rho GTPases is conserved in all eukaryotic cell types

7. Organization of the Actin Cytoskeleton The fibers and filaments of the cytokeleton mediate a variety of essential biological processes including cytokinesis and cell migration. Proper function of the cytoskeleton is necessary for wound healing, axonal outgrowth, embryonic development, and lymphocyte migration to the sites of infection. Rho and Cdc42 are required late in the cell cycle for formation of the actin myosin contractile ring

8. Rho Involvement in Gene Transcription Rho, Rac, and Cdc42 have all been reported to regulate the JNK and MAP kinase cascades (Hall, 1998). This means that they regulate gene transcription in even a more direct way than through their effects on adhesion complexes (Hall, 1998). Evidence for other mechanisms in which Rho family proteins directly stimulate gene transcription have also been reported (Hall, 1998). Specifically, these reports show that independent of JNK and MAP kinase cascades, the GTPases stimulate transcription from a cyclin D promoter, activating serum response transcription factor, SRF (Hall, 1998).

9. Motif Search ound in Initiation factor 2 (matches 131 proteins) GTP-binding nuclear protein Ran (matches 130 proteins) Tetracycline-resistance protein (matches 58 proteins) GTP-binding protein, HSR1-related (matches 361 proteins) Ferrous iron transport protein B (matches 62 proteins) Ras small GTPase, Ras type (matches 353 proteins) Ras small GTPase, Rho type (matches 379 proteins) Ras small GTPase, Rab type (matches 745 proteins) tRNA modification GTPase TrmE (matches 87 proteins) Translation elongation factor, selenocysteine-specific (matches 20 proteins) Translation elongation factor G (matches 130 proteins) Translation elongation factor Tu (matches 263 proteins) Translation elongation factor aEF-2 (matches 24 proteins) Translation initiation factor aIF-2 (matches 15 proteins) Peptide chain release factor 3 (matches 50 proteins) GTP-binding protein Era (matches 82 proteins) GTP1/OBG sub-domain (matches 201 proteins) GTP-binding protein LepA (matches 85 proteins) GTP-binding protein TypA (matches 67 proteins) GTP-binding protein SAR1 (matches 64 proteins)

10. Multiple Sequence Alignment The predicted amino acid sequence of the protein is very similar to those of various members of the RAS superfamily of low molecular weight GTP-binding proteins, including NRAS, KRAS, HRAS, and the RHO proteins.

12. Implication in Malignant Cancers CDC42 plays a role in activating the pathway to transcription of a gene leading to progression of the cell cycle (G1 to S phase of cell life cycle). It receives signals from integrins and passes the signal on. Integrin receptors can tell a cell if it is anchored properly. If CDC42 is mutated to always be on then cells can grow without being anchored properly. For this reason, CDC42 is linked to tumor growth and metastasis.

13. Overexpression of Cdx1 in IEC-6 cells leads to adenocarcinoma development via activation of Ras, Cdc42 and PI3 kinase pathways.

14. Sources