Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

PML tumor suppressor is regulated by HIPK2-mediated phosphorylation in response to DNA damage.

Gresko, Ekaterina and Ritterhoff, S and Sevilla-Perez, J and Roscic, Ana and Froebius, K and Kotevic, I and Vichalkovski, A and Hess, Daniel and Hemmings, Brian Arthur and Schmitz, M L (2009) PML tumor suppressor is regulated by HIPK2-mediated phosphorylation in response to DNA damage. Oncogene, 28 (5). pp. 698-708. ISSN 1476-5594

Abstract

The promyelocytic leukemia (PML) tumor suppressor protein, a central regulator of cell proliferation and apoptosis, is frequently fused to the retinoic acid receptor-alpha (RARalpha) in acute PML. Here we show the interaction of PML with another tumor suppressor protein, the serine/threonine kinase homeodomain-interacting protein kinase (HIPK2). In response to DNA damage, HIPK2 phosphorylates PML at serines 8 and 38. Although HIPK2-mediated phosphorylation of PML occurs early during the DNA damage response, the oncogenic PML-RARalpha fusion protein is phosphorylated with significantly delayed kinetics. DNA damage or HIPK2 expression leads to the stabilization of PML and PML-RARalpha proteins. The N-terminal phosphorylation sites contribute to the DNA damage-induced PML SUMOylation and are required for the ability of PML to cooperate with HIPK2 for the induction of cell death.

Item Type: Article
Related URLs:
Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: HIPK2; PML; phosphorylation; cell death
Related URLs:
Date Deposited: 14 Dec 2009 13:50
Last Modified: 31 Jan 2013 01:01
URI: https://oak.novartis.com/id/eprint/973

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.