Abstract
The (11;19)(q23;p13.1) translocation in acute leukemia results in the formation of a chimeric MLL-ELL fusion protein. ELL is an RNA Polymerase II (Pol II) transcriptional elongation factor that interacts with the recently identified EAF1 protein. Here, we show that ELL and EAF1 are components of Cajal bodies (CBs). Although ELL and EAF1 colocalize with p80 coilin, the signature protein of CBs, ELL and EAF1 do not exhibit a direct physical interaction with p80 coilin. Treatment of cells with actinomycin D, DRB, or alpha-amanitin, specific inhibitors of Pol II, disperses ELL and EAF1 from CBs, indicating that localization of ELL and EAF1 in CBs is dependent on active transcription by Pol II. The concentration of ELL and EAF1 in CBs links the transcriptional elongation activity of ELL to the RNA processing functions previously identified in CBs. Strikingly, CBs are disrupted in MLL-ELL leukemia. EAF1 and p80 coilin are delocalized from CBs in murine MLL-ELL leukemia cells and in HeLa cells transiently transfected with MLL-ELL. Nuclear and cytoplasmic fractionation revealed diminished expression of p80 coilin and EAF1 in the nuclei of MLL-ELL leukemia cells [corrected]. These studies are the first demonstration of a direct role of CB components in leukemogenesis.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Autoantigens
-
Cell Line
-
Chromosomal Proteins, Non-Histone / metabolism
-
Chromosomes, Human, Pair 11 / genetics
-
Chromosomes, Human, Pair 19 / genetics
-
Coiled Bodies / metabolism*
-
DNA-Binding Proteins / metabolism*
-
HeLa Cells
-
Humans
-
Leukemia, Myeloid, Acute / genetics
-
Leukemia, Myeloid, Acute / metabolism*
-
Myeloid-Lymphoid Leukemia Protein
-
Neoplasm Proteins*
-
Nuclear Proteins / metabolism
-
Oncogene Proteins, Fusion / genetics
-
Oncogene Proteins, Fusion / metabolism
-
Peptide Elongation Factors*
-
Phosphoproteins / metabolism
-
RNA / biosynthesis
-
Recombinant Proteins / genetics
-
Recombinant Proteins / metabolism
-
Ribonucleoproteins, Small Nuclear / metabolism
-
Transcription Factors / metabolism*
-
Transcriptional Elongation Factors
-
Transfection
-
Translocation, Genetic
-
snRNP Core Proteins
Substances
-
Autoantigens
-
Chromosomal Proteins, Non-Histone
-
DNA-Binding Proteins
-
EAF1 protein, human
-
ELL protein, human
-
MLL-ELL fusion protein, human
-
NOLC1 protein, human
-
Neoplasm Proteins
-
Nuclear Proteins
-
Oncogene Proteins, Fusion
-
Peptide Elongation Factors
-
Phosphoproteins
-
Recombinant Proteins
-
Ribonucleoproteins, Small Nuclear
-
Transcription Factors
-
Transcriptional Elongation Factors
-
fibrillarin
-
snRNP Core Proteins
-
p80-coilin
-
Myeloid-Lymphoid Leukemia Protein
-
RNA