Distinct effects of mitogens and the actin cytoskeleton on CREB and pocket protein phosphorylation control the extent and timing of cyclin A promoter activity.
نویسندگان
چکیده
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 the organized actin cytoskeleton to regulate the duration of ERK signaling, the expression of cyclin D1, and the timing of pocket protein phosphorylation.
منابع مشابه
Timing of Cyclin A Promoter Activity Phosphorylation Control the Extent and Cytoskeleton on CREB and Pocket Protein Distinct Effects of Mitogens and the Actin
متن کامل
O-13: Na+/K+-ATPase Alpha1 Isoform Mediates Ouabain-Induced Expression of Cyclin D1 and Proliferation of Rat Sertoli Cells
Background: Novel roles for the interaction of cardiotonic steroids to Na+/K+-ATPase have been established in recent years. The aim of the present study was to investigate the intracellular signaling events downstream the action of ouabain on Na+/K+-ATPase in Sertoli cell obtained from immature rats. Treatment of Sertoli cells with ouabain (1 μM) induced a rapid and transient increase in the ex...
متن کاملProstacylin receptor activation inhibits proliferation of aortic smooth muscle cells by regulating cAMP response element-binding protein- and pocket protein-dependent cyclin a gene expression.
The prostanoid prostacyclin (PGI2) inhibits aortic smooth muscle cell proliferation by blocking cell cycle progression from G1-to S-phase. However, the mechanism of this inhibition is poorly understood. We report here that the PGI2 mimetic, cicaprost, inhibits the induction of cyclin A and activation of the cyclin A promoter in primary and established rodent aortic smooth muscle cells. The inhi...
متن کاملTranscriptional Coactivator CBP Facilitates Transcription Initiation and Reinitiation of HTLV-I and Cyclin D2 Promoter
HTLV-I is the etiologic agent for adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Taxi, the major activator of this virus, is a 40- kDa (353 amino acid) phosphoprotein, predominantly localized in the nucleus of the host cell, which functions to trans-activate both viral and cellular promoters. Recently it has been shown that HTLV-I a...
متن کاملStudy of the role of CREB, BDNF, and VGF neuropeptide in long term antidepressant activity of crocin in the rat cerebellum
Antidepressant activity of crocin, saffron main component, has been established before. Based on previous study, it is suggested that elevation in the levels of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide could be considered as one probable molecular mechanisms involved in antidepressant activity of long term crocin administration in the r...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Molecular and cellular biology
دوره 21 22 شماره
صفحات -
تاریخ انتشار 2001