Exogenous expression of a dominant negative RORa1 vector in muscle cells impairs differentiation: RORa1 directly interacts with p300 and MyoD

Lau, Patrick, Bailey, Peter, Dowhan, Dennis H. and Muscat, George E. O. (1999) Exogenous expression of a dominant negative RORa1 vector in muscle cells impairs differentiation: RORa1 directly interacts with p300 and MyoD. Nucleic Acids Research, 27 2: 411-420. doi:10.1093/nar/27.2.411

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Author Lau, Patrick
Bailey, Peter
Dowhan, Dennis H.
Muscat, George E. O.
Title Exogenous expression of a dominant negative RORa1 vector in muscle cells impairs differentiation: RORa1 directly interacts with p300 and MyoD
Journal name Nucleic Acids Research   Check publisher's open access policy
ISSN 1362-4962
0305-1048
Publication date 1999-01
Sub-type Article (original research)
DOI 10.1093/nar/27.2.411
Open Access Status DOI
Volume 27
Issue 2
Start page 411
End page 420
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 1999
Language eng
Abstract ROR/RZR is an orphan nuclear receptor that has no known ligand in the 'classical sense'. In the present study we demonstrate that RORalpha is constitutively expressed during the differentiation of proliferating myoblasts to post-mitotic multinucleated myotubes, that have acquired a contractile phenotype. Exogenous expression of dominant negative RORalpha1DeltaE mRNA in myogenic cells significantly reduces the endogenous expression of RORalpha1 mRNA, represses the accumu-lation and delays the activation of mRNAs encoding MyoD and myogenin [the muscle-specific basic helix-loop-helix (bHLH) proteins] and p21(Waf- 1/Cip-1) (a cdk inhibitor). Immunohistochemistry demonstrates that morpho-logical differentiation is delayed in cells expressing the RORDeltaE transcript. Furthermore, the size and development of mutlinucleated myotubes is impaired. The E region of RORalpha1 interacts with p300, a cofactor that functions as a coactivator in nuclear receptor and MyoD-mediated transactivation. Consistent with the functional role of RORalpha1 in myogenesis, we observed that RORalpha1 directly interacts with the bHLH protein MyoD. This interaction was mediated by the N-terminal activation domain of the bHLH protein, MyoD, and the RORalpha1 DNA binding domain/C region. Furthermore, we demonstrated that p300, RORalpha1 and MyoD interact in a non- competitive manner. In conclusion, this study provides evidence for a biological role and positive influence of RORalpha1 in the cascade of events involved in the activation of myogenic-specific markers and cell cycle regulators and suggests that crosstalk between theretinoid- relatedorphan (ROR) nuclear receptors and the myogenic bHLH proteins has functional consequences for differentiation.
Q-Index Code C1
Institutional Status UQ

 
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