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

Katia Todoerti, Domenica Ronchetti, Luca Agnelli, Stefano Castellani, Silvia Marelli, Giorgio Lambertenghi Deliliers, Alberto Zanella, Luigia Lombardi, Antonino Neri

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)214-218
Number of pages5
JournalBritish Journal of Haematology
Volume131
Issue number2
DOIs
Publication statusPublished - Oct 2005

Keywords

  • MMSET
  • Multiple myeloma
  • Transcriptional regulation

ASJC Scopus subject areas

  • Hematology

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