Transcriptional regulation of cyclin D2 by the PKA pathway and inducible cAMP early repressor in granulosa cells.

Biology of Reproduction
Luis C MuñizCarlos A Molina

Abstract

Cyclin D2 (Ccnd2) is an essential gene for folliculogenesis, as null mutation in mice impairs granulosa cell proliferation in response to FSH. Ccnd2 mRNA is induced during the estrus cycle by FSH and is rapidly inhibited by LH. Yet, the responsive elements and transcription factors accounting for the gene expression of cyclin D2 in the ovary have not been fully characterized. Using primary cultures of rat granulosa cells and immortalized mouse granulosa cells, we demonstrate a mechanism for the regulation of cyclin D2 at the level of transcription via a PKA-dependent signaling mechanism. The promoter activity of cyclin D2 was shown to be induced by FSH and the catalytic alpha subunit of PKA (PRKACA), and this activity was repressible by inducible cAMP early repressor (ICER), a cAMP response element (CRE) modulator isoform. In silico analysis of the mouse, rat, and human cyclin D2 promoters identified two CRE-binding protein sites, a conserved proximal element and a less conserved distal element relative to the translation start site. The mutation on the proximal element drastically decreases the effects of PRKACA and ICER on the promoter activity, whereas the mutation on the distal element did not contribute to the decrease in ...Continue Reading

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Citations

Sep 11, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Alexander P SobinoffEileen A McLaughlin
Jul 26, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Alexander P SobinoffEileen A McLaughlin
Apr 24, 2008·The Journal of Clinical Investigation·Rodger E TiedemannA Keith Stewart
Nov 22, 2007·Proceedings of the National Academy of Sciences of the United States of America·Tao XieLee S Weinstein
Aug 21, 2012·Canadian Journal of Physiology and Pharmacology·Adam HotchkissKishore B S Pasumarthi
Jun 12, 2008·Diabetes·Woo-Jin SongMehboob A Hussain
Sep 4, 2016·Biochemical and Biophysical Research Communications·Luis C Muñiz, Carlos A Molina
Apr 30, 2017·International Journal of Molecular Sciences·Livio CasariniManuela Simoni
Aug 31, 2018·Minerva ginecologica·Laura RiccettiManuela Simoni
Feb 23, 2021·Cancer Treatment and Research Communications·Jan PawlonkaUrszula Ambroziak

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BETA
PCR
transfection
Immunoprecipitation
electrophoresis
Footprinting
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transgenic

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