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Molecular and Cellular Biology, April 2009, p. 1814-1825, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.00585-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Protein Kinase C-Dependent Phosphorylation Regulates the Cell Cycle-Inhibitory Function of the p73 Carboxy Terminus Transactivation Domain{triangledown} ,{dagger}

Ulrika Nyman,1,{ddagger} Pinelopi Vlachos,1,{ddagger} Anna Cascante,2 Ola Hermanson,2 Boris Zhivotovsky,1 and Bertrand Joseph1*

Institute of Environmental Medicine,1 Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden2

Received 10 April 2008/ Returned for modification 15 June 2008/ Accepted 11 January 2009

The transcription factor p73, a member of the p53 family of proteins, is involved in the regulation of cell cycle progression and apoptosis. However, the regulatory mechanisms controlling the distinct roles for p73 in these two processes have remained unclear. Here, we report that p73 is able to induce cell cycle arrest independently of its amino-terminal transactivation domain, whereas this domain is crucial for p73 proapoptotic functions. We also characterized a second transactivation domain in the carboxy terminus of p73 within amino acid residues 381 to 399. This carboxy terminus transactivation domain was found to preferentially regulate genes involved in cell cycle progression. Moreover, its activity is regulated throughout the cell cycle and modified by protein kinase C-dependent phosphorylation at serine residue 388. Our results suggest that this novel posttranslational modification within the p73 carboxy terminus transactivation domain is involved in the context-specific guidance of p73 toward the selective induction of cell cycle arrest.

* Corresponding author. Present address: Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Phone: 46-8-524 87 556. Fax: 46-8-32 90 41. E-mail: Bertrand.Joseph{at}ki.se

{triangledown} Published ahead of print on 21 January 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, SE-171 76 Stockholm, Sweden.

Molecular and Cellular Biology, April 2009, p. 1814-1825, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.00585-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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