PML tumor suppressor is regulated by HIPK2-mediated phosphorylation in response to DNA damage.
Tools
Tools
Gresko, Ekaterina, Ritterhoff, S, Sevilla-Perez, J, Roscic, Ana, Froebius, K, Kotevic, I, Vichalkovski, A, Hess, Daniel, 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 |