MAGE-A1 interacts with adaptor SKIP and the deacetylase HDAC1 to repress transcription.
(2004) Nucleic Acids Research — Vol. 32, n° 14, p. 4340-4350 (2004)
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- 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.
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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 (Original work published 2004)