Muscle cell survival mediated by the transcriptional co-activators p300 and PCAF

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Am J Physiol Cell Physiol. 2006 May 3

Muscle cell survival mediated by the transcriptional co-activators

p300 and PCAF displays different requirements for acetyl-transferase

activity.

Kuninger D, A, Rotwein P.

Biochemistry and Molecular Biology, Oregon Health & Science

University, Portland, Oregon, United States.

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

co-activators p300 and PCAF. We previously described C2 skeletal

myoblasts lacking expression of insulin-like growth factor-II (IGF-

II), which underwent progressive apoptotic death when incubated in

differentiation-promoting medium. Viability of these cells was

sustained by addition of IGF analogues 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 acetyl-transferase 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

micro-array 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 acetyl-transferase activity, and acts at least

in part through FGF-1.