The tumor suppressor WARTS activates the Omi / HtrA2-dependent pathway of cell death.

Abstract:

:Drosophila tumor suppressor WARTS (Wts) is an evolutionally conserved serine / threonine kinase and participates in a signaling complex that regulates both proliferation and apoptosis to ensure the proper size and shape of the fly. Human counterparts of this complex have been found to be frequently downregulated or mutated in cancers. WARTS, a human homolog of Wts, is also known as tumor suppressor and mitotic regulator, but its molecular implications in tumorigenesis are still obscure. Here, we show that WARTS binds via its C-terminus to the PDZ domain of a proapoptotic serine protease Omi / HtrA2. Depletion of WARTS inhibited Omi / HtrA2-mediated cell death, whereas overexpression of WARTS promoted this process. Furthermore, WARTS can enhance the protease activity of Omi / HtrA2 both in vivo and in vitro. Activation of Omi / HtrA2-mediated cell death is thus a potential mechanism for the tumor suppressive activity of WARTS.

journal_name

Oncogene

journal_title

Oncogene

authors

Kuninaka S,Nomura M,Hirota T,Iida S,Hara T,Honda S,Kunitoku N,Sasayama T,Arima Y,Marumoto T,Koja K,Yonehara S,Saya H

doi

10.1038/sj.onc.1208682

subject

Has Abstract

pub_date

2005-08-11 00:00:00

pages

5287-98

issue

34

eissn

0950-9232

issn

1476-5594

pii

1208682

journal_volume

24

pub_type

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