In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 16 ( 2003-08-05), p. 9524-9529
Abstract:
p300 and cAMP response element binding protein (CREB)-binding protein (CBP)
are two highly homologous, conserved transcriptional coactivators, and histone acetyltransferases (HATs) that link chromatin remodeling with transcription.
Cell transformation by viral oncogene products such as adenovirus E1A and SV40 large T antigen depends on their ability to inactivate p300 and CBP. To
investigate the role of p300 in cell-cycle progression, we constructed stable rat cell lines, which conditionally overexpress p300 from a
tetracycline-responsive promoter. When p300 was induced in these
cells, serum-stimulated S-phase entry was significantly inhibited. The inhibition of S-phase induction was associated with down-regulation of c-Myc , but not of c-Fos or c-Jun . Simultaneous
overexpression of c-Myc and p300 before serum stimulation
reversed the inhibition of S-phase induction to a significant level, indicating that the inhibition of c-Myc to a large extent is
responsible for the p300 inhibition of G 1 exit. Similar studies
with stable rat cell lines that overexpress a mutant p300, which lacks the HAT activity, showed that the intrinsic HAT activity of p300 is not required for
the negative regulation of c-Myc or G 1 . These findings,
and our previously published results (Kolli, S., Buchmann, A. M., Williams, J., Weitzman, S. & Thimmapaya, B. (2001) Proc. Natl. Acad. Sci.
USA 98, 4646–4651), establish an important negative regulatory role
for p300 in c-Myc expression that may be important in maintaining the
cells in the G 0 /G 1 phase of the cell cycle.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1633700100
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2003
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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