This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bottazzi, M. E.
Right arrow Articles by Assoian, R. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bottazzi, M. E.
Right arrow Articles by Assoian, R. K.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2001, p. 7607-7616, Vol. 21, No. 22
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.22.7607-7616.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Distinct Effects of Mitogens and the Actin Cytoskeleton on CREB and Pocket Protein Phosphorylation Control the Extent and Timing of Cyclin A Promoter Activity

Maria Elena Bottazzi,1 Monica Buzzai,1 Xiaoyun Zhu,1,dagger Chantal Desdouets,2 Christian Bréchot,2 and Richard K. Assoian1,*

Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6084,1 and Institut National de la Santé et de la Recherche Médicale U370, Faculté Necker, 75742 Paris Cedex 15, France2

Received 3 April 2001/Returned for modification 8 May 2001/Accepted 13 August 2001

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 G1-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.

* Corresponding author. Mailing address: Department of Pharmacology, University of Pennsylvania School of Medicine, 167 Johnson Pavilion, 3620 Hamilton Walk, Philadelphia, PA 19104-6084. Phone: (215) 898-7157. Fax: (215) 573-5656. E-mail: rka{at}pharm.med.upenn.edu.

dagger Present address: Sunol Molecular Corp., Miramar, Fla.

Molecular and Cellular Biology, November 2001, p. 7607-7616, Vol. 21, No. 22
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.22.7607-7616.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Ignatova, I. D., Kostadinova, R. M., Goldring, C. E., Nawrocki, A. R., Frey, F. J., Frey, B. M. (2009). Tumor necrosis factor-{alpha} upregulates 11{beta}-hydroxysteroid dehydrogenase type 1 expression by CCAAT/enhancer binding protein-{beta} in HepG2 cells. Am. J. Physiol. Endocrinol. Metab. 296: E367-E377 [Abstract] [Full Text]  
  • Cheng, J. C., Kinjo, K., Judelson, D. R., Chang, J., Wu, W. S., Schmid, I., Shankar, D. B., Kasahara, N., Stripecke, R., Bhatia, R., Landaw, E. M., Sakamoto, K. M. (2008). CREB is a critical regulator of normal hematopoiesis and leukemogenesis. Blood 111: 1182-1192 [Abstract] [Full Text]  
  • Margadant, C., van Opstal, A., Boonstra, J. (2007). Focal adhesion signaling and actin stress fibers are dispensable for progression through the ongoing cell cycle. J. Cell Sci. 120: 66-76 [Abstract] [Full Text]  
  • Li, H., Chi, C.-Y., Lee, S., Andrisani, O. M. (2006). The Mitogenic Function of Hepatitis B Virus X Protein Resides within Amino Acids 51 to 140 and Is Modulated by N- and C-Terminal Regulatory Regions. J. Virol. 80: 10554-10564 [Abstract] [Full Text]  
  • Croft, D. R., Olson, M. F. (2006). The Rho GTPase Effector ROCK Regulates Cyclin A, Cyclin D1, and p27Kip1 Levels by Distinct Mechanisms. Mol. Cell. Biol. 26: 4612-4627 [Abstract] [Full Text]  
  • Fassett, J., Tobolt, D., Hansen, L. K. (2006). Type I Collagen Structure Regulates Cell Morphology and EGF Signaling in Primary Rat Hepatocytes through cAMP-dependent Protein Kinase A. Mol. Biol. Cell 17: 345-356 [Abstract] [Full Text]  
  • Fortemaison, N., Blancquaert, S., Dumont, J. E., Maenhaut, C., Aktories, K., Roger, P. P., Dremier, S. (2005). Differential Involvement of the Actin Cytoskeleton in Differentiation and Mitogenesis of Thyroid Cells: Inactivation of Rho Proteins Contributes to Cyclic Adenosine Monophosphate-Dependent Gene Expression but Prevents Mitogenesis. Endocrinology 146: 5485-5495 [Abstract] [Full Text]  
  • Crespo, J., Martinez-Gonzalez, J., Rius, J., Badimon, L. (2005). Simvastatin inhibits NOR-1 expression induced by hyperlipemia by interfering with CREB activation. Cardiovasc Res 67: 333-341 [Abstract] [Full Text]  
  • Bill, H. M., Knudsen, B., Moores, S. L., Muthuswamy, S. K., Rao, V. R., Brugge, J. S., Miranti, C. K. (2004). Epidermal Growth Factor Receptor-Dependent Regulation of Integrin-Mediated Signaling and Cell Cycle Entry in Epithelial Cells. Mol. Cell. Biol. 24: 8586-8599 [Abstract] [Full Text]  
  • Rius, J., Martinez-Gonzalez, J., Crespo, J., Badimon, L. (2004). Involvement of Neuron-Derived Orphan Receptor-1 (NOR-1) in LDL-Induced Mitogenic Stimulus in Vascular Smooth Muscle Cells: Role of CREB. Arterioscler. Thromb. Vasc. Bio. 24: 697-702 [Abstract] [Full Text]  
  • Zuckerbraun, B. S., Shapiro, R. A., Billiar, T. R., Tzeng, E. (2003). RhoA Influences the Nuclear Localization of Extracellular Signal-Regulated Kinases to Modulate p21Waf/Cip1 Expression. Circulation 108: 876-881 [Abstract] [Full Text]  
  • Kothapalli, D., Stewart, S. A., Smyth, E. M., Azonobi, I., Rader, D. J., Pure, E., Assoian, R. K. (2003). Prostacylin Receptor Activation Inhibits Proliferation of Aortic Smooth Muscle Cells by Regulating cAMP Response Element-Binding Protein- and Pocket Protein-Dependent Cyclin A Gene Expression. Mol. Pharmacol. 64: 249-258 [Abstract] [Full Text]  
  • Brar, S. S., Corbin, Z., Kennedy, T. P., Hemendinger, R., Thornton, L., Bommarius, B., Arnold, R. S., Whorton, A. R., Sturrock, A. B., Huecksteadt, T. P., Quinn, M. T., Krenitsky, K., Ardie, K. G., Lambeth, J. D., Hoidal, J. R. (2003). NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells. Am. J. Physiol. Cell Physiol. 285: C353-C369 [Abstract] [Full Text]  
  • Roovers, K., Assoian, R. K. (2003). Effects of Rho Kinase and Actin Stress Fibers on Sustained Extracellular Signal-Regulated Kinase Activity and Activation of G1 Phase Cyclin-Dependent Kinases. Mol. Cell. Biol. 23: 4283-4294 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»