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protein phosphatase 6 catalytic subunit OKDB#: 5259
 Symbols: PPP6C Species: human
 Synonyms: PP6, PP6C  Locus: 9q33.3 in Homo sapiens


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General Comment NCBI Summary: This gene encodes the catalytic subunit of protein phosphatase, a component of a signaling pathway regulating cell cycle progression. Splice variants encoding different protein isoforms exist. The pseudogene of this gene is located on chromosome X. [provided by RefSeq, Jul 2008]
General function Enzyme
Comment
Cellular localization Cytoplasmic
Comment
Ovarian function Initiation of primordial follicle growth, Oocyte maturation
Comment
Expression regulated by
Comment
Ovarian localization Oocyte
Comment
Follicle stages
Comment
Phenotypes
Mutations 2 mutations

Species: mouse
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: Loss of protein phosphatase 6 in oocytes causes failure of meiosis II exit and impaired female fertility. Hu MW et al. (2015) Dynamic protein phosphorylation and dephosphorylation, mediated by a conserved cohort of protein kinases or phosphatases, regulate cell cycle progression. Among the well-known PP2A-like protein phosphatases, PP6 has been analyzed in mammalian mitosis recently identifying Aurora A as its key substrate. However, the functions of PP6 in meiosis are still entirely unknown. To identify the physiological role of PP6 in female gametogenesis, Ppp6c(F/F) mice were first generated and crossed with Zp3-Cre mice to selectively disrupt Ppp6c expression in oocytes. Here we report for the first time that PP6c was dispensable for oocyte meiotic maturation but essential for MII exit after fertilization, since depletion of PP6c caused abnormal MII spindle and disrupted MII cytokinesis, resulting in zygotes with high risk of aneuploidy, defective early embryonic development, thus severe subfertility. We also revealed that PP6 inactivation interfered with MII spindle formation and MII exit due to increased Aurora A activity, and Aurora A inhibition with MLN8237 could rescue the PP6c depletion phenotype. In conclusion, our findings uncover a hitherto unknown role for PP6 as an indispensable regulator of oocyte meiosis and female fertility.//////////////////

Species: mouse
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: Protein Phosphatase 6 Protects Prophase I-Arrested Oocytes by Safeguarding Genomic Integrity. Hu MW et al. (2016) Mammalian oocytes are arrested at prophase of the first meiotic division in the primordial follicle pool for months, even years, after birth depending on species, and only a limited number of oocytes resume meiosis, complete maturation, and ovulate with each reproductive cycle. We recently reported that protein phosphatase 6 (PP6), a member of the PP2A-like subfamily, which accounts for cellular serine/threonine phosphatase activity, functions in completing the second meiosis. Here, we generated mutant mice with a specific deletion of Ppp6c in oocytes from the primordial follicle stage by crossing Ppp6cF/F mice with Gdf9-Cre mice and found that Ppp6cF/F; GCre+ mice are infertile. Deletion of PP6c caused folliculogenesis defects and germ cell loss independent of the traditional AKT/mTOR pathway, but due to persistent phosphorylation of H2AX (a marker of double strand breaks), increased susceptibility to DNA damage and defective DNA repair, which led to massive oocyte elimination and eventually premature ovarian failure (POF). Our findings uncover an important role for PP6 as an indispensable guardian of genomic integrity of the lengthy prophase I oocyte arrest, maintenance of primordial follicle pool, and thus female fertility.//////////////////

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Phenotypes and GWAS show phenotypes and GWAS
Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
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created: Sept. 28, 2015, 1:48 p.m. by: system   email:
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last update: Dec. 12, 2016, 4:32 p.m. by: hsueh    email:



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