E2F-1 regulates the expression of a subset of target genes during skeletal myoblast hypertrophy

17Citations
Citations of this article
11Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Cellular hypertrophy, or growth without division, is an adaptive response to various physiological and pathological stimuli in postmitotic muscle. We demonstrated previously that angiotensin II stimulates hypertrophy in C2C12 myoblasts by transient activation of the cyclin-dependent kinase 4 complex, subsequent phosphorylation of retinoblastoma protein, release of histone deacetylase 1 from the retinoblastoma protein inhibitory complex, and partial activation of the transcription factor E2F-1. These observations led us to propose a model in which partial inactivation of the retinoblastoma protein complex leads to the derepression of a subset of E2F-1 targets necessary for cell growth without division during hypertrophy. We now present data that support this model and suggest the mechanism by which E2F-1 regulates hypertrophy. We examined expression profiles of angiotensin II-stimulated myoblasts and identified a subset of E2F-1 target genes that are specifically regulated during the hypertrophic response. We showed that the expression of E2F-1 targets involved in G1/S transit, DNA replication, and mitosis is not altered during the hypertrophic response, while the expression of E2F-1-regulated genes controlling early G1 progression, cytoskeletal organization, protein synthesis, mitochondrial function, and programmed cell death is up-regulated. Furthermore, we demonstrated that activation of cytochrome c oxidase genes occurs during the development of hypertrophy and that cytochrome c oxidase IV is a direct transcriptional target of E2F-1. These studies demonstrated that E2F-1 activity at specific promoters is dependent on physiological circumstances and that E2F-1 should be considered a potential target in the treatment of pathologic hypertrophy.

Cite

CITATION STYLE

APA

Hlaing, M., Spitz, P., Padmanabhan, K., Cabezas, B., Barker, C. S., & Bernstein, H. S. (2004). E2F-1 regulates the expression of a subset of target genes during skeletal myoblast hypertrophy. Journal of Biological Chemistry, 279(42), 43625–43633. https://doi.org/10.1074/jbc.M408391200

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free