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PMID: 20159561 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia.

Molecular cell ·Vol. 37 ·No. 3 ·2010-02-12 ·Pages 429-37

Lin C, Smith ER, Takahashi H, Lai KC, Martin-Brown S, Florens L, Washburn MP, Conaway JW, Conaway RC, Shilatifard A

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.

MeSH Terms
Amino Acid Sequence Animals Cell Line, Tumor Drosophila Proteins/genetics,metabolism,physiology HSP70 Heat-Shock Proteins/metabolism HeLa Cells Heat-Shock Response Histone-Lysine N-Methyltransferase Homeobox A10 Proteins Homeodomain Proteins/metabolism Humans Leukemia/genetics Molecular Sequence Data Myeloid-Lymphoid Leukemia Protein/genetics,physiology Positive Transcriptional Elongation Factor B/metabolism RNA Interference Repressor Proteins/genetics,metabolism,physiology Sequence Alignment Transcription, Genetic Transcriptional Elongation Factors/metabolism,physiology Translocation, Genetic
Chemicals
AFF4 protein, human Drosophila Proteins ELL protein, human HSP70 Heat-Shock Proteins Homeobox A10 Proteins Homeodomain Proteins KMT2A protein, human Repressor Proteins Transcriptional Elongation Factors homeobox protein HOXA9 HOXA10 protein, human Myeloid-Lymphoid Leukemia Protein Histone-Lysine N-Methyltransferase Positive Transcriptional Elongation Factor B
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Lin Chengqi
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Smith Edwin R
Takahashi Hidehisa
Lai Ka Chun
Martin-Brown Skylar
Florens Laurence
Washburn Michael P
Conaway Joan W
Conaway Ronald C
Shilatifard Ali
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2010.01.026
Published
2010-02-12
Pages
429-37
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC2872029
Subset
IM
Grants
NCI NIH HHS · R01 CA089455 · United States
NCI NIH HHS · R01CA089455-10 · United States
NCI NIH HHS · R01 CA089455-09 · United States
NIGMS NIH HHS · R01 GM041628 · United States
NIGMS NIH HHS · R37 GM041628 · United States
NCI NIH HHS · R01 CA150265 · United States
NIGMS NIH HHS · R37 GM041628-22 · United States
NIGMS NIH HHS · R01 GM041628-24 · United States
Corrections
CommentIn
PMID: 20188661
External Links
PubMed source DOI: 10.1016/j.molcel.2010.01.026 PMC Full Text View journal details
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