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HPMR

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Protease, Serine, 25 OKDB#: 3069
 Symbols: PRSS25 Species: human
 Synonyms: OMI, PRSS25,HTRA, E. COLI, HOMOLOG OF, 2, HTRA2|OMI  Locus: 2p12 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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General Comment NCBI Summary: This gene encodes a serine protease. The protein has been localized in the endoplasmic reticulum and interacts with an alternatively spliced form of mitogen-activated protein kinase 14. The protein has also been localized to the mitochondria with release to the cytosol following apoptotic stimulus. The protein is thought to induce apoptosis by binding the apoptosis inhibitory protein baculoviral IAP repeat-containing 4. Nuclear localization of this protein has also been observed. Alternate splicing of this gene results in two transcript variants encoding different isoforms. Additional transcript variants have been described, but their full-length sequences have not been determined.
General function Apoptosis, Enzyme
Comment
Cellular localization Mitochondrial, ER
Comment
Ovarian function Follicle atresia
Comment ROLE AND REGULATION OF NODAL/ALK7 SIGNALING PATHWAY IN THE CONTROL OF OVARIAN FOLLICULAR ATRESIA. Wang H et al. Although the role of the transforming growth factor (TGF) beta superfamily members in the regulation of ovarian folliculogenesis has been extensively studied, their involvement in follicular atresia is not well understood. In the present study, we have demonstrated for the first time that Nodal, a member of the TGF beta superfamily, is involved in promoting follicular atresia as evidenced by: (a) Co-localization of Nodal and its type I receptor ALK7 proteins in the granulosa cells was only observed in atretic antral follicles, while they were present in theca cells and granulosa cells of healthy follicles, respectively; (b) Addition of recombinant Nodal or over-expression of Nodal by adenoviral infection induced apoptosis of otherwise healthy granulosa cells; (c) Constitutively active ALK7 (ALK7-ca) over-expression mimicked the function of Nodal in the induction of granulosa cell apoptosis. Furthermore, over-expression of Nodal or ALK7-ca increased phosphorylation and nuclear translocation of Smad2, decreased Xiap expression at both mRNA and protein level and phospho-Akt content, as well as triggered mitochondrial release of death proteins Smac/DIABLO, Omi/HtrA2 and cytochrome c in the granulosa cells. Dominant negative-Smad2 significantly attenuated ALK7-ca-induced down-regulation of Xiap and thus rescued granulosa cells from undergoing apoptosis. In addition, while up-regulation of Xiap significantly attenuated ALK7-ca-induced apoptosis, down-regulation of Xiap sensitized granulosa cells to ALK7-ca-induced apoptosis. Furthermore, ALK7-ca-induced apoptosis was significantly attenuated by forced expression of activated Akt, and Akt rescued granulosa cells from undergoing apoptosis via proteasome-mediated ALK7 degradation. Taken together, Nodal plays an atretogenic role in the ovary where it induces granulosa cell apoptosis through activation of Smad2, down-regulation of the key survival molecules Xiap and phospho-Akt, as well as the activation of mitochondrial death pathway.
Expression regulated by
Comment
Ovarian localization Granulosa
Comment
Follicle stages
Comment
Phenotypes
Mutations 0 mutations
Genomic Region show genomic region
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: May 24, 2006, 6:39 a.m. by: hsueh   email:
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last update: May 26, 2006, 2:27 p.m. by: rami    email:



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