Pc. Zuzarte et al., Tumor cell splice variants of the transcription factor TEF-1 induced by SV40 T-antigen transformation, BBA-GENE ST, 1517(1), 2000, pp. 82-90
Citations number
47
Categorie Soggetti
Molecular Biology & Genetics
Journal title
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
The large tumor antigen (TAg) of simian virus 40 is able to transform cells
through interactions with cellular proteins, notably p53 and Rb. Among the
other proteins that form complexes with TAg is TEF-1, a transcription fact
or utilized by the viral enhancer to activate expression of the early gene
which encodes TAg. We show that fibroblasts contain several alternately spl
iced TEF-1 mRNAs, the most abundant of which encodes a protein with an addi
tional four amino acid exon compared to the database entry for Hela cell TE
F-1. Transformation by TAg induces alternate splicing, producing a more abu
ndant form lacking this exon and matching the published sequence. Splicing
variants lacking this exon were detected in mouse pancreatic tumors and in
cell lines derived from human pancreatic cancers, in contrast to a single i
soform with the exon in normal mouse pancreas. A total of eight splice vari
ants were identified, with the loss of the four amino acid exon typical of
transformed cells. These and other data presented suggest that TAg 're-mode
ls' host cell transcription factors that are used early in viral infection,
and thereby mimics an event that naturally occurs during transformation. T
he data indicate that TEF-1 alterations may be a hallmark feature of tumori
genesis. (C) 2000 Elsevier Science B.V. All rights reserved.