PPM1D (Wip) is a serine/threonine phosphatase implicated in cell cycle control, spermatogenesis, and lymphoid cell function. The predicted 605-amino acid PPM1D protein contains 2 putative nuclear localization signals and 3 regions conserved in serine/threonine PP2C phosphatases, as well as characteristics of a type 2C phosphatase, including magnesium dependence and relative insensitivity to okadaic acid. PPM1D expression is induced in response to ionizing radiation in a p53-dependent manner. The accumulation of PPM1D mRNA following ionizing radiation is rapid and transient, and PPM1D protein is localized to the nucleus. PPM1D may contribute to growth inhibitory pathways activated in response to DNA damage in a p53-dependent manner. PPM1D inhibits phosphorylation of the p38 mitogen-activated (MAP)kinase protein. Through p38 MAPK, PPM1D modulates the CDKN2A tumor-suppressor locus. This gene is located in a chromosomal region known to be amplified in breast cancer, (located at 17q22-q23), is amplified in human breast tumor cell lines and in approximately 11% of primary breast tumors, and appears to lead to cell transformation by abrogating p53 tumor suppressor activity. Inactivation of the p38 MAPK through PPM1D overexpression resulting from PPM1D amplification may contributes to the development of human cancers by suppressing p53 activation. PPM1D null mice have increased susceptibility to pathogens and reduced male fertility and longevity.
Function:
Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins.
Subunit:
Interacts with CHEK1 and CHEK2; dephosphorylates them.
Similarity:
Belongs to the PP2C family.
Contains 1 PP2SLClike domain.
SWISS:
O15297
Gene ID:
8493
Database links:
Entrez Gene: 8493 Human
Entrez Gene: 53892 Mouse
Entrez Gene: 380383 Xenopus laevis
Entrez Gene: 394065 Zebrafish
Omim: 605100 Human
SwissProt: O15297 Human
SwissProt: Q5RI25 Mouse
SwissProt: Q9QZ67 Mouse
Unigene: 286073 Human
Unigene: 45609 Mouse
Wip1是一种镁依赖性的丝氨酸/苏氨酸蛋白磷酸酶,属于蛋白磷酸酶2C家族。Wip1通过p53诱导在癌症的发生、发展中起到重要作用,在多种人类癌细胞中都已发现Wip1的大量扩增和过量存在。
| Picture |
Sample:
Hela(Human) Cell Lysate at 30 ug
Primary: Anti-PPM1D (SL2447R) at 1/500 dilution
Secondary: IRDye800CW Goat Anti-Rabbit IgG at 1/20000 dilution
Predicted band size: 67 kD
Observed band size: 67 kD
|
|
|
