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
Oncogenejournal_title
Oncogeneauthors
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 Hdoi
10.1038/sj.onc.1208682subject
Has Abstractpub_date
2005-08-11 00:00:00pages
5287-98issue
34eissn
0950-9232issn
1476-5594pii
1208682journal_volume
24pub_type
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