Transcription repression activity is associated with the type I isoform of the MMSET gene involved in t(4;14) in multiple myeloma.

The WHSC1/MMSET gene, involved in t(4;14)(p16.3;q32) in multiple myeloma, encodes putative isoforms (MMSET I, MMSET II and RE-IIBP) which are thought to be involved in transcription regulation. We investigated their activity in transfected 293T and HeLa cells. Both MMSET I and MMSET II were localised in the nucleus, whereas RE-IIBP ...
showed cytoplasmic and nucleolar staining. MMSET I dose-dependently repressed the transcriptional activity of the promoter region of the thymidine kinase gene, whereas MMSET II and RE-IIBP had no effect. The HDAC inhibitor, trichostatin A, reduced MMSET I repression activity and in vitro co-immunoprecipitation analyses indicated that MMSET I specifically recruits HDAC1 and mSin3b, but not HDAC2 or HDAC4. Our data support the hypothesis that MMSET may act as a transcription regulator; different functions may be associated with distinct isoforms.
Mesh Terms:
Carrier Proteins, Cell Line, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 4, Gene Deletion, Gene Expression Regulation, Neoplastic, Genes, Regulator, Hela Cells, Histone-Lysine N-Methyltransferase, Humans, Multiple Myeloma, Protein Isoforms, Protein Structure, Tertiary, Repressor Proteins, Transcription, Genetic
Br. J. Haematol.
Date: Oct. 01, 2005
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