Transcript Document

CELL DIVISION CYCLE 42
CDC42 a low molecular weight GTP-binding protein
originally designated G(p) and also called G25K
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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.
CDC4 Gene
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Ensembl Gene Report
Stable ID: ENST00000315545 Exons: 6
bp Translation length: 191 residues
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Link
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Transcript length: 2106
http://www.ensembl.org/Homo_sapiens/geneview?gene=ENSG00000070831
Rittinger, K. et al.
(1997). Nature,
This is the
crystalized
structure of Cdc42
bound to a nonhydrolyzable GTP
analog
Function
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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
Organization of the Actin
Cytoskeleton
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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.
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Rho and Cdc42 are required late in the cell cycle for formation of the actin
myosin contractile ring
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).
Motif Search
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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)
Multiple Sequence Alignment
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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.
Implication in Malignant Cancers
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CDC42 plays a role in activating the
pathway to transcription of a gene leading
to progression of the cell cycle (G1 to S
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It receives signals from integrins and
passes the signal on.
phase of cell life cycle).
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.
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Overexpression of Cdx1
in IEC-6 cells leads to
adenocarcinoma
development via
activation of Ras, Cdc42
and PI3 kinase
pathways.
Sources