M-phase inducer phosphatase 1 also known as dual specificity phosphatase Cdc25A is a
protein that in humans is encoded by the cell division cycle 25 homolog A (CDC25A)
gene.
All mammals examined to date have three homologues of the ancestral Cdc25 gene (found e.g. in the
fungus species S. pombe), designated Cdc25A, Cdc25B, and Cdc25C. In contrast, some invertebrates harbour two (e.g., the Drosophila proteins String and Twine) or four (e.g., C. elegans Cdc-25.1 - Cdc-25.4) homologues.
CDC25A is required for progression from G1 to the S phase of the
cell cycle, but also plays roles in later cell cycle events. In particular, it is stabilized in metaphase cells and is degraded upon metaphase exit akin to
Cyclin B. It is competent to activate the G1/S cyclin-dependent kinases
CDK4 and
CDK2 by removing inhibitory phosphate groups from adjacent
tyrosine and
threonine residues; it can also activate
Cdc2 (Cdk1), the principal mitotic Cdk.
Involvement in cancer
CDC25A is specifically degraded in response to
DNA damage, resulting in cell cycle arrest. Thus, this degradation represents one axis of a DNA damage
checkpoint, complementing induction of
p53 and
p21 in the inhibition of
CDKs.
CDC25A is considered an
oncogene, as it can cooperate with oncogenic
RAS to transform rodent fibroblasts, and it is overexpressed in tumours from a variety of tissues, including breast and head & neck tumours. It is a target of the
E2F family of transcription factors. Therefore, its overexpression is a common consequence of dysregulation of the
p53-
p21-
Cdk axis in
carcinogenesis.[5]
^Huang TS, Shu CH, Yang WK, Whang-Peng J (Jul 1997). "Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331-induced apoptosis". Cancer Res. 57 (14): 2974–8.
PMID9230211.
^Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H, Elledge SJ (Sep 1997). "Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25". Science. 277 (5331): 1497–501.
doi:
10.1126/science.277.5331.1497.
PMID9278511.
Huang TS, Shu CH, Yang WK, Whang-Peng J (1997). "Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331-induced apoptosis". Cancer Res. 57 (14): 2974–8.
PMID9230211.
M-phase inducer phosphatase 1 also known as dual specificity phosphatase Cdc25A is a
protein that in humans is encoded by the cell division cycle 25 homolog A (CDC25A)
gene.
All mammals examined to date have three homologues of the ancestral Cdc25 gene (found e.g. in the
fungus species S. pombe), designated Cdc25A, Cdc25B, and Cdc25C. In contrast, some invertebrates harbour two (e.g., the Drosophila proteins String and Twine) or four (e.g., C. elegans Cdc-25.1 - Cdc-25.4) homologues.
CDC25A is required for progression from G1 to the S phase of the
cell cycle, but also plays roles in later cell cycle events. In particular, it is stabilized in metaphase cells and is degraded upon metaphase exit akin to
Cyclin B. It is competent to activate the G1/S cyclin-dependent kinases
CDK4 and
CDK2 by removing inhibitory phosphate groups from adjacent
tyrosine and
threonine residues; it can also activate
Cdc2 (Cdk1), the principal mitotic Cdk.
Involvement in cancer
CDC25A is specifically degraded in response to
DNA damage, resulting in cell cycle arrest. Thus, this degradation represents one axis of a DNA damage
checkpoint, complementing induction of
p53 and
p21 in the inhibition of
CDKs.
CDC25A is considered an
oncogene, as it can cooperate with oncogenic
RAS to transform rodent fibroblasts, and it is overexpressed in tumours from a variety of tissues, including breast and head & neck tumours. It is a target of the
E2F family of transcription factors. Therefore, its overexpression is a common consequence of dysregulation of the
p53-
p21-
Cdk axis in
carcinogenesis.[5]
^Huang TS, Shu CH, Yang WK, Whang-Peng J (Jul 1997). "Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331-induced apoptosis". Cancer Res. 57 (14): 2974–8.
PMID9230211.
^Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H, Elledge SJ (Sep 1997). "Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25". Science. 277 (5331): 1497–501.
doi:
10.1126/science.277.5331.1497.
PMID9278511.
Huang TS, Shu CH, Yang WK, Whang-Peng J (1997). "Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331-induced apoptosis". Cancer Res. 57 (14): 2974–8.
PMID9230211.