RGD Reference Report - Regulation of the expression of prostate apoptosis response protein 4 (Par-4) in rat granulosa cells. - Rat Genome Database

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Regulation of the expression of prostate apoptosis response protein 4 (Par-4) in rat granulosa cells.

Authors: Gonzalez, IH  Santana, P  Gonzalez-Robayna, I  Ferrer, M  Morales, V  Blanco, FL  Fanjul, LF 
Citation: Gonzalez IH, etal., Apoptosis. 2007 Apr;12(4):769-79.
RGD ID: 9835345
Pubmed: PMID:17219052   (View Abstract at PubMed)
DOI: DOI:10.1007/s10495-006-0019-7   (Journal Full-text)

The par-4 gene, directs the expression of a protein in the rat ventral prostate after apoptotic stimuli but not growth stimulatory, growth arresting or necrotic signals. Since Par-4 expression appears to be ubiquitous we investigated the possibility of Par-4 having a role in the rat ovary granulosa cells apoptotic death. Par-4 mRNA was detected by RT-PCR with oligonucleotides designed to prime Par-4 leucine zipper in the ovaries of 12 day old rats and reached the higher levels in 24 days old rats. In situ hybridization analysis revealed that Par-4 expression is restricted to granulosa cells. PMSG priming of 24 day old rats for 2 days greatly reduced Par-4 expression in granulosa cells as determined by in situ hybridization, RT-PCR of mRNA and protein immunodetection with Western blot. Granulosa cells placed in serum-fee culture, exhibited increased levels of Par-4 mRNA and protein, in good correlation with the degree of apoptosis. The culture-induced increases in Par-4 are significantly prevented by FSH. Transient transfection of granulosa cells with Par-4 leucine zipper domain that functions as a dominant-negative regulator of Par-4 activity resulted in lower rates of apoptosis while overexpression of the full length Par-4 counteracted FSH effects on apoptosis. Par-4 association with PKCzeta which is supposed to inhibit this kinase mediated antiapoptotic way is also prevented by FSH and, FSH antiapoptotic effects are counteracted by a PKCzeta specific inhibitor. These findings indicate that FSH by suppressing Par-4 expression in the ovary activates PKCzeta-dependent antiapoptotic pathway and suggest that Par-4 is part of the mechanism underlying granulosa cells apoptotic demise.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to follicle-stimulating hormone stimulus  IEP 9835345 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPIPawr (Rattus norvegicus)9835345 RGD 
protein kinase C binding  IPIPrkcz (Rattus norvegicus)9835345 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pawr  (pro-apoptotic WT1 regulator)
Prkcz  (protein kinase C, zeta)


Additional Information