Muscle cell survival mediated by the transcriptional coactivators p300 and PCAF displays different requirements for acetyltransferase activity

David Kuninger, Alistair Wright, Peter Rotwein

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Normal skeletal muscle development requires the proper orchestration of genetic programs by myogenic regulatory factors (MRFs). The actions of the MRF protein MyoD are enhanced by the transcriptional coactivators p300 and the p300/CBP-associated factor (PCAF). We previously described C2 skeletal myoblasts lacking expression of insulin-like growth factor-II (IGF-II) that underwent progressive apoptotic death when incubated in differentiation-promoting medium. Viability of these cells was sustained by addition of IGF analogs or unrelated peptide growth factors. We now show that p300 or PCAF maintains myoblast viability as effectively as added growth factors through mechanisms requiring the acetyltransferase activity of PCAF but not of p300. The actions of p300 to promote cell survival were not secondary to increased expression of known MyoD targets, as evidenced by results of gene microarray experiments, but rather appeared to be mediated by induction of other genes, including fibroblast growth factor-1 (FGF-1). Conditioned culture medium from cells expressing p300 increased myoblast viability, and this was blocked by pharmacological inhibition of FGF receptors. Our results define a role for p300 in promoting cell survival, which is independent of its acetyltransferase activity and acts at least in part through FGF-1.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume291
Issue number4
DOIs
StatePublished - 2006

Fingerprint

Acetyltransferases
Myogenic Regulatory Factors
Muscle Cells
Muscle
Fibroblast Growth Factor 1
Cell Survival
Myoblasts
Cells
Intercellular Signaling Peptides and Proteins
MyoD Protein
Skeletal Myoblasts
Fibroblast Growth Factor Receptors
Insulin-Like Growth Factor II
Muscle Development
Genes
Conditioned Culture Medium
Skeletal Muscle
Microarrays
Pharmacology
Peptides

Keywords

  • Fibroblast growth factor-I
  • Microarray
  • Myoblast

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Muscle cell survival mediated by the transcriptional coactivators p300 and PCAF displays different requirements for acetyltransferase activity. / Kuninger, David; Wright, Alistair; Rotwein, Peter.

In: American Journal of Physiology - Cell Physiology, Vol. 291, No. 4, 2006.

Research output: Contribution to journalArticle

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