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1: Br J Haematol. 2005 Oct;131(2):214-8.Click here to read Links

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

Todoerti K, Ronchetti D, Agnelli L, Castellani S, Marelli S, Deliliers GL, Zanella A, Lombardi L, Neri A.

U.O. Ematologia 2, Centro Trapianti di Midollo, Dipartimento di Scienze Mediche, Università degli Studi di Milano, Ospedale Maggiore IRCCS Milano, Milan, Italy.

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.

PMID: 16197452 [PubMed - indexed for MEDLINE]