AFF4, a Component of the ELL/P-TEFb Elongation Complex and a Shared Subunit of MLL Chimeras, Can Link Transcription Elongation to Leukemia

Chengqi Lin, Edwin R. Smith, Hidehisa Takahashi, Ka Chun Lai, Skylar Martin-Brown, Laurence Florens, Michael P. Washburn, Joan W. Conaway, Ronald C. Conaway, Ali Shilatifard*

*Corresponding author for this work

Research output: Contribution to journalArticle

348 Scopus citations

Abstract

Chromosomal translocations involving the MLL gene are associated with infant acute lymphoblastic and mixed lineage leukemia. There are a large number of translocation partners of MLL that share very little sequence or seemingly functional similarities; however, their translocations into MLL result in the pathogenesis of leukemia. To define the molecular reason why these translocations result in the pathogenesis of leukemia, we purified several of the commonly occurring MLL chimeras. We have identified super elongation complex (SEC) associated with all chimeras purified. SEC includes ELL, P-TEFb, AFF4, and several other factors. AFF4 is required for SEC stability and proper transcription by poised RNA polymerase II in metazoans. Knockdown of AFF4 in leukemic cells shows reduction in MLL chimera target gene expression, suggesting that AFF4/SEC could be a key regulator in the pathogenesis of leukemia through many of the MLL partners.

Original languageEnglish (US)
Pages (from-to)429-437
Number of pages9
JournalMolecular cell
Volume37
Issue number3
DOIs
StatePublished - Feb 12 2010

Keywords

  • HUMDISEASE
  • PROTEINS
  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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