Antisense-mediated depletion of p300 in human cells leads to premature G(1) exit and up-regulation of c-MYC

The cAMP-response element-binding protein (CREB)-binding protein and p300 are two highly conserved transcriptional coactivators and histone acetyltransferases that integrate signals from diverse signal transduction pathways in the nucleus and also link chromatin remodeling with transcription. In thi...

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Hlavní autoři: Kolli, Sivanagarani, Buchmann, Ann Marie, Williams, Justin, Weitzman, Sigmund, Thimmapaya, Bayar
Médium: Článek
Jazyk:en
Vydáno: National Academy of Sciences 2001
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Biological Sciences
On-line přístup:https://ncbi.nlm.nih.gov/pmc/articles/PMC31888/
https://ncbi.nlm.nih.gov/pubmed/11296295
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1073/pnas.081141998
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spelling pubmed-318882001-05-22 Antisense-mediated depletion of p300 in human cells leads to premature G(1) exit and up-regulation of c-MYC Kolli, Sivanagarani Buchmann, Ann Marie Williams, Justin Weitzman, Sigmund Thimmapaya, Bayar Proc Natl Acad Sci U S A Biological Sciences The cAMP-response element-binding protein (CREB)-binding protein and p300 are two highly conserved transcriptional coactivators and histone acetyltransferases that integrate signals from diverse signal transduction pathways in the nucleus and also link chromatin remodeling with transcription. In this report, we have examined the role of p300 in the control of the G(1) phase of the cell cycle in nontransformed immortalized human breast epithelial cells (MCF10A) and fibroblasts (MSU) by using adenovirus vectors expressing p300-specific antisense sequences. Quiescent MCF10A and MSU cells expressing p300-specific antisense sequences synthesized p300 at much reduced levels and exited G(1) phase without serum stimulation. These cells also showed an increase in cyclin A and cyclin A- and E-associated kinase activities characteristic of S phase induction. Further analysis of the p300-depleted quiescent MCF10A cells revealed a 5-fold induction of c-MYC and a 2-fold induction of c-JUN. A direct target of c-MYC, CAD, which is required for DNA synthesis, was also found to be up-regulated, indicating that up-regulation of c-MYC functionally contributed to DNA synthesis. Furthermore, S phase induction in p300-depleted cells was reversed when antisense c-MYC was expressed in these cells, indicating that up-regulation of c-MYC may directly contribute to S phase induction. Adenovirus E1A also induced DNA synthesis and increased the levels of c-MYC and c-JUN in serum-starved MCF10A cells in a p300-dependent manner. Our results suggest an important role of p300 in cell cycle regulation at G(1) and raise the possibility that p300 may negatively regulate early response genes, including c-MYC and c-JUN, thereby preventing DNA synthesis in quiescent cells. National Academy of Sciences 2001-04-10 /pmc/articles/PMC31888/ /pubmed/11296295 http://dx.doi.org/10.1073/pnas.081141998 Text en Copyright © 2001, The National Academy of Sciences
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Biological Sciences
spellingShingle Biological Sciences
Kolli, Sivanagarani
Buchmann, Ann Marie
Williams, Justin
Weitzman, Sigmund
Thimmapaya, Bayar
Antisense-mediated depletion of p300 in human cells leads to premature G(1) exit and up-regulation of c-MYC
description The cAMP-response element-binding protein (CREB)-binding protein and p300 are two highly conserved transcriptional coactivators and histone acetyltransferases that integrate signals from diverse signal transduction pathways in the nucleus and also link chromatin remodeling with transcription. In this report, we have examined the role of p300 in the control of the G(1) phase of the cell cycle in nontransformed immortalized human breast epithelial cells (MCF10A) and fibroblasts (MSU) by using adenovirus vectors expressing p300-specific antisense sequences. Quiescent MCF10A and MSU cells expressing p300-specific antisense sequences synthesized p300 at much reduced levels and exited G(1) phase without serum stimulation. These cells also showed an increase in cyclin A and cyclin A- and E-associated kinase activities characteristic of S phase induction. Further analysis of the p300-depleted quiescent MCF10A cells revealed a 5-fold induction of c-MYC and a 2-fold induction of c-JUN. A direct target of c-MYC, CAD, which is required for DNA synthesis, was also found to be up-regulated, indicating that up-regulation of c-MYC functionally contributed to DNA synthesis. Furthermore, S phase induction in p300-depleted cells was reversed when antisense c-MYC was expressed in these cells, indicating that up-regulation of c-MYC may directly contribute to S phase induction. Adenovirus E1A also induced DNA synthesis and increased the levels of c-MYC and c-JUN in serum-starved MCF10A cells in a p300-dependent manner. Our results suggest an important role of p300 in cell cycle regulation at G(1) and raise the possibility that p300 may negatively regulate early response genes, including c-MYC and c-JUN, thereby preventing DNA synthesis in quiescent cells.
author Kolli, Sivanagarani
Buchmann, Ann Marie
Williams, Justin
Weitzman, Sigmund
Thimmapaya, Bayar
author_facet Kolli, Sivanagarani
Buchmann, Ann Marie
Williams, Justin
Weitzman, Sigmund
Thimmapaya, Bayar
author_sort Kolli, Sivanagarani
title Antisense-mediated depletion of p300 in human cells leads to premature G(1) exit and up-regulation of c-MYC
title_short Antisense-mediated depletion of p300 in human cells leads to premature G(1) exit and up-regulation of c-MYC
title_full Antisense-mediated depletion of p300 in human cells leads to premature G(1) exit and up-regulation of c-MYC
title_fullStr Antisense-mediated depletion of p300 in human cells leads to premature G(1) exit and up-regulation of c-MYC
title_full_unstemmed Antisense-mediated depletion of p300 in human cells leads to premature G(1) exit and up-regulation of c-MYC
title_sort antisense-mediated depletion of p300 in human cells leads to premature g(1) exit and up-regulation of c-myc
publisher National Academy of Sciences
publisher_facet National Academy of Sciences
publishDate 2001
url https://ncbi.nlm.nih.gov/pmc/articles/PMC31888/
https://ncbi.nlm.nih.gov/pubmed/11296295
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1073/pnas.081141998
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