Activation of the tumor-specific death effector apoptin and its kinase by an N-terminal determinant of simian virus 40 large T antigen.

Abstract:

:Apoptin, a viral death protein derived from chicken anemia virus, displays a number of tumor-specific behaviors. In particular, apoptin is phosphorylated, translocates to the nucleus, and induces apoptosis specifically in tumor or transformed cells, whereas it is nonphosphorylated and remains primarily inactive in the cytoplasm of nontransformed normal cells. Here, we show that in normal cells apoptin can also be activated by the transient transforming signals conferred by ectopically expressed simian virus 40 (SV40) large T antigen (LT), which rapidly induces apoptin's phosphorylation, nuclear accumulation, and the ability to induce apoptosis. Further analyses with mutants of LT showed that the minimum domain capable of inducing all three of apoptin's tumor-specific properties resided in the N-terminal J domain, a sequence which is largely shared by SV40 small t antigen (st). Interestingly, the J domain in st, which lacks its own nuclear localization signal (NLS), required nuclear localization to activate apoptin. These results reveal the existence of a cellular pathway shared by conditions of transient transformation and the stable cancerous or precancerous state, and they support a model whereby a transient transforming signal confers on apoptin both the upstream activity of phosphorylation and the downstream activity of nuclear accumulation and apoptosis induction. Such a pathway may reflect a general lesion contributing to human cancers.

journal_name

J Virol

journal_title

Journal of virology

authors

Zhang YH,Kooistra K,Pietersen A,Rohn JL,Noteborn MH

doi

10.1128/JVI.78.18.9965-9976.2004

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

9965-76

issue

18

eissn

0022-538X

issn

1098-5514

pii

78/18/9965

journal_volume

78

pub_type

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