Distinct effects of mitogens and the actin cytoskeleton on CREB and pocket protein phosphorylation control the extent and timing of cyclin A promoter activity

Molecular and Cellular Biology
M E BottazziRichard K Assoian

Abstract

Soluble mitogens and adhesion-dependent organization of the actin cytoskeleton are required for cells to enter S phase in fibroblasts. The induction of cyclin A is also required for S-phase entry, and we now report that distinct effects of mitogens and the actin cytoskeleton on the phosphorylation of CREB and pocket proteins regulate the extent and timing of cyclin A promoter activity, respectively. First, we show that CREB phosphorylation and binding to the cyclic AMP response element (CRE) determines the extent, but not the timing, of cyclin A promoter activity. Second, we show that pocket protein inactivation regulates the timing, but not the extent, of cyclin A promoter activity. CREB phosphorylation and CRE occupancy are regulated by soluble mitogens alone, while the phosphorylation of pocket proteins requires both mitogens and the organized actin cytoskeleton. Mechanistically, cytoskeletal integrity controls pocket protein phosphorylation by allowing for sustained ERK signaling and, thereby, the expression of cyclin D1. Our results lead to a model of cyclin A gene regulation in which mitogens play a permissive role by stimulating early G(1)-phase phosphorylation of CREB and a distinct regulatory role by cooperating with t...Continue Reading

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Citations

Aug 29, 2012·Cellular and Molecular Life Sciences : CMLS·Coert MargadantJohannes Boonstra
Aug 13, 2011·Histochemistry and Cell Biology·Maarten J A MoesJohannes Boonstra
Jun 2, 2006·Molecular and Cellular Biology·Daniel R Croft, Michael F Olson
Nov 3, 2007·Blood·Jerry C ChengKathleen M Sakamoto
Jun 3, 2009·Free Radical Biology & Medicine·William C Burhans, Nicholas H Heintz
Feb 1, 2005·Virus Research·G Joan GrindlayVincent O'Brien
Feb 18, 2004·The Journal of Clinical Investigation·Devashish KothapalliRichard K Assoian
Mar 18, 2015·Medical Microbiology and Immunology·Deborah H Spector
Dec 18, 2008·American Journal of Physiology. Endocrinology and Metabolism·Irena D IgnatovaBrigitte M Frey
Apr 11, 2003·American Journal of Physiology. Cell Physiology·Sukhdev S BrarJohn R Hoidal

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