NDLI: Chk2 regulates irradiation-induced, p53-mediated apoptosis in Drosophila

Content Provider	PubMed Central
Author	Peters, Malte Deluca, Carmela Hirao, Atsushi Stambolic, Vuk Potter, Julia Zhou, Lily Liepa, Jennifer Snow, Bryan Arya, Sudha Wong, Jorge Bouchard, Denis Richard, Binari Manoukian, Armen S. Mak, Tak W.
Copyright Year	2002
Abstract	The tumor suppressor function of p53 has been attributed to its ability to regulate apoptosis and the cell cycle. In mammals, DNA damage, aberrant growth signals, chemotherapeutic agents, and UV irradiation activate p53, a process that is regulated by several posttranslational modifications. In Drosophila melanogaster, however, the regulation modes of p53 are still unknown. Overexpression of D. melanogaster p53 (Dmp53) in the eye induced apoptosis, resulting in a small eye phenotype. This phenotype was markedly enhanced by coexpression with D. melanogaster Chk2 (DmChk2) and was almost fully rescued by coexpression with a dominant-negative (DN), kinase-dead form of DmChk2. DN DmChk2 also inhibited Dmp53-mediated apoptosis in response to DNA damage, whereas overexpression of Grapes (Grp), the Drosophila Chk1-homolog, and its DN mutant had no effect on Dmp53-induced phenotypes. DmChk2 also activated the Dmp53 transactivation activity in cultured cells. Mutagenesis of Dmp53 amino terminal Ser residues revealed that Ser-4 is critical for its responsiveness toward DmChk2. DmChk2 activates the apoptotic activity of Dmp53 and Ser-4 is required for this effect. Contrary to results in mammals, Grapes, the Drosophila Chk1-homolog, is not involved in regulating Dmp53. Chk2 may be the ancestral regulator of p53 function.
Related Links	http://dx.doi.org/10.1073/pnas.172382899
Ending Page	11310
Page Count	6
Starting Page	11305
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	17
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-08-20
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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Chk2 regulates irradiation-induced, p53-mediated apoptosis in Drosophila.

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