MAGE-A1 interacts with adaptor SKIP and the deacetylase HDAC1 to repress transcription

Sandra Laduron, Rachel Deplus, Sifang Zhou, Olga Kholmanskikh, Danièle Godelaine, Charles De Smet, S. Diane Hayward, François Fuks, Thierry Boon, Etienne De Plaen

Research output: Contribution to journalArticle

Abstract

MAGE-A1 belongs to a family of 12 genes that are active in various types of tumors and silent in normal tissues except in male germ-line cells. The MAGE-encoded antigens recognized by T cells are highly tumor-specific targets for T cell-oriented cancer immunotherapy. The function of MAGE-A1 is currently unknown. To analyze it, we attempted to identify protein partners of MAGE-A1. Using yeast two-hybrid screening, we detected an interaction between MAGE-A1 and Ski Interacting Protein (SKIP). SKIP is a transcriptional regulator that connects DNA-binding proteins to proteins that either activate or repress transcription. We show that MAGE-A1 inhibits the activity of a SKIP-interacting transactivator, namely the intracellular part of Notch1. Deletion analysis indicated that this inhibition requires the binding of MAGE-A1 to SKIP. Moreover, MAGE-A1 was found to actively repress transcription by binding and recruiting histone deacetylase 1 (HDAC1). Our results indicate that by binding to SKIP and by recruiting HDACs, MAGE-A1 can act as a potent transcriptional repressor. MAGE-A1 could therefore participate in the setting of specific gene expression patterns for tumor cell growth or spermatogenesis.

Original languageEnglish (US)
Pages (from-to)4340-4350
Number of pages11
JournalNucleic acids research
Volume32
Issue number14
DOIs
StatePublished - Sep 27 2004

ASJC Scopus subject areas

  • Genetics

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    Laduron, S., Deplus, R., Zhou, S., Kholmanskikh, O., Godelaine, D., De Smet, C., Hayward, S. D., Fuks, F., Boon, T., & De Plaen, E. (2004). MAGE-A1 interacts with adaptor SKIP and the deacetylase HDAC1 to repress transcription. Nucleic acids research, 32(14), 4340-4350. https://doi.org/10.1093/nar/gkh735