A novel repressor domain is required for maximal growth inhibition by the IRF-1 tumor suppressor

Eckert, M., Meek, S. E.M. and Ball, K. L. (2006) A novel repressor domain is required for maximal growth inhibition by the IRF-1 tumor suppressor. Journal of Biological Chemistry, 281(32), pp. 23092-23102. (doi: 10.1074/jbc.M512589200)

Abstract

Interferon regulatory factor-1 (IRF-1) is a transcription factor and tumor suppressor that can regulate gene expression in a manner requiring either its sequence specific DNA binding activity or its ability to bind the p300 coactivator. We show that IRF-1-mediated growth inhibition is dependent on the integrity of a C-terminal transcriptional enhancer domain. An enhancer subdomain (amino acids 301-325) that differentially regulates IRF-1 activity has been identified and this region mediates the repression of Cdk2. The repressor domain encompasses an LXXLL coregulator signature motif and mutations or deletions within this region completely uncouple transcriptional activation from repression. The loss of growth suppressor activity when the Cdk2-repressor domain of IRF-1 is mutated implicates repression as a determinant of its maximal growth inhibitory potential. The data link IRF-1 regulatory domains to its growth inhibitory activity and provide information about how differential gene regulation may contribute to IRF-1 tumor suppressor activity.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Meek, Dr Sarah
• Authors: Eckert, M., Meek, S. E.M., and Ball, K. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Biological Chemistry
• Journal Abbr.: J Biol Chem.
• Publisher: American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258
• ISSN (Online): 1083-351X