Publication: SV40 early region oncoproteins
and human cell transformation
Authors
Chen, W. ; Hahn, W.C.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
We now understand neoplastic
transformation to be the consequence of multiple
acquired genetic alterations. The combination of these
acquired changes confer the various phenotypes that
constitute the clinical features of cancer. Although only
rare human cancers derive from a viral etiology, the
study of DNA tumor viruses that transform rodent and
human cells has led to a greater understanding of the
molecular events that program the malignant state. In
particular, investigation of the viral oncoproteins
specified by the Simian Virus 40 Early Region (SV40
ER) has revealed critical host cell pathways, whose
perturbation play an essential role in the experimental
transformation of mammalian cells. Recent work has reinvestigated
the roles of two SV40 ER oncoproteins, the
large T antigen (LT) and the small t antigen (ST), in
human cell transformation. Co-expression of these two
oncoproteins, together with the telomerase catalytic
subunit, hTERT, and an oncogenic version of the H-Ras
oncoprotein, suffices to transform human cells. LT
inactivates two key tumor suppressor pathways by
binding to the retinoblastoma protein (pRB) and p53.
The ability of ST to transform human cells requires
interactions with PP2A, an abundant family of serinethreonine
phosphatases. Here we review recent
developments in our understanding of how these two
viral oncoproteins facilitate human cell transformation.
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