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Different functions are required for initiation and maintenance of immortalization of rat embryo fibroblasts by SV40 large T antigen.

Abstract：

:We have used two different, but complementary assays to characterize functions of SV40 T antigen that are necessary for its ability to immortalize rat embryo fibroblasts. In accordance with previous work, we found that several functions were required. These include activities that map to the p53 binding domain and the amino terminal 176 amino acids which contain the J domain as well as the CR1 and CR2 domain required for binding and sequestering the RB family of pocket proteins. Moreover, we found that even though activities dependent only upon the amino terminus were sufficient for immortalization they were unable to maintain it. This suggests that immortalization by these amino terminal functions requires either additional events or immortalization of a subset of cells within the heterogeneous rat embryo fibroblast population. We further found that an activity dependent upon amino acids 17 - 27 which remove a portion of the CR1 domain and the predicted alpha-1 helix of the J domain was not necessary to maintain growth but was required for direct immortalization suggesting that at least one of the functions required initially was not required to maintain the immortal state. This represents the first demonstration that some of the functions required for maintenance of the immortal state differ from those required for initiation of immortalization.

journal_name

Oncogene

journal_title

Oncogene

authors

Powell AJ,Darmon AJ,Gonos ES,Lam EW,Peden KW,Jat PS

doi

10.1038/sj.onc.1203154

subject

Has Abstract

pub_date

1999-12-02 00:00:00

pages

7343-50

issue

51

eissn

0950-9232

issn

1476-5594

journal_volume

18

pub_type

杂志文章

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