Adenovirus E1A products suppress myogenic differentiation and inhibit transcription from muscle-specific promoters (original) (raw)

Nature volume 332, pages 553–557 (1988)Cite this article

Abstract

The primary function of the adenovirus ElA-region genes is to activate other adenoviral genes during a permissive viral infection by modifying the host cell transcriptional apparatus1,2. Host cell immortalization, or transformation by the whole adenoviral early region, presumably results as a consequence of these modifications. Both transcriptional activation and transcriptional repression of non-adenoviral genes by the E1A proteins have been reported3–9. It is currently not clear which, if either, of these activities contributes to host cell transformation and immortalization. Although there may be a physiological impact of some ElA-stimulated host cell genes10–12, in many cases the functional significance is unclear, No common target sequences have been recognized in stimulated cellular genes and it has recently been proposed that in many cases, particularly involving newly transfected genes, available 'TATA-box' sequences may be the opportunistic beneficiaries of ElA assistance as a secondary consequence of ElA primary functions within the host cell nucleus1,13. ElA-mediated transcriptional repression appears to be a more specific process insofar as common core elements are shared by the ElA-suppressed SV40, polyoma B, IgG heavy-chain and insulin enhancers_9_. In the present communication we report that the complete myogenic programme of L8 and C2 myoblasts can be blocked by the introduction of constitutively expressing ElA genes, and show that the transcriptional induction of muscle-specific genes is inhibited. In particular, the promoter-inducing activities of well-defined elements that are required for the muscle-specific expression of the two sarcomeric a-actins, and which normally bind cellular _trans_-acting factors, become targets for E1A suppression. The results support the hypothesis that the suppression of differentiation by ElA products is effected by an ElA-mediated block in the transcriptional activation of cellular genes by specific developmentally regulated _cis_-acting promoter elements.

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Authors and Affiliations

  1. The Medigen Project, Stanford University School of Medicine and Veterans Administration Medical Center, 151M, 3801 Miranda Avenue, Palo Alto, California, 94304, USA
    Keith A. Webster, George E. O. Muscat & Larry Kedes

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  1. Keith A. Webster
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  2. George E. O. Muscat
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  3. Larry Kedes
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Webster, K., Muscat, G. & Kedes, L. Adenovirus E1A products suppress myogenic differentiation and inhibit transcription from muscle-specific promoters.Nature 332, 553–557 (1988). https://doi.org/10.1038/332553a0

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