The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis.

Abstract	MLL is involved in chromosomal rearrangements that generate fusion proteins with deregulated transcriptional activity. The mechanisms of MLL fusion protein-mediated transcriptional activation are poorly understood. Here we show MLL interacts directly with the polymerase associated factor complex (PAFc) through sequences flanking the CxxC domain. PAFc interacts with RNA polymerase II and stimulates posttranslational histone modifications. PAFc augments MLL and MLL-AF9 mediated transcriptional activation of Hoxa9. Conversely, knockdown of PAFc disrupts MLL fusion protein-mediated transcriptional activation and MLL recruitment to target loci. PAFc gene expression is downregulated during hematopoiesis and likely serves to regulate MLL function. Deletions of MLL that abolish interactions with PAFc also eliminate MLL-AF9 mediated immortalization indicating an essential function for this interaction in leukemogenesis.
Authors	Andrew G Muntean, Jiaying Tan, Kajal Sitwala, Yongsheng Huang, Joel Bronstein, James A Connelly, Venkatesha Basrur, Kojo S J Elenitoba-Johnson, Jay L Hess
Journal	Cancer cell (Cancer Cell) Vol. 17 Issue 6 Pg. 609-21 (Jun 15 2010) ISSN: 1878-3686 [Electronic] United States
PMID	20541477 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	CDC73 protein, human CTR9 protein, human Carrier Proteins DNA-Binding Proteins E2a-Hlf fusion protein, human Homeodomain Proteins LEO1 protein, human MLL-AF9 fusion protein, human MLL-ENL oncoprotein, human Myeloid Ecotropic Viral Integration Site 1 Protein Neoplasm Proteins Nuclear Proteins Oncogene Proteins, Fusion PAF1 protein, human Phosphoproteins RNA polymerase II associated factor 1, mouse Recombinant Proteins Transcription Factors Tumor Suppressor Proteins homeobox protein HOXA9 Myeloid-Lymphoid Leukemia Protein DNA
Topics	Animals Carrier Proteins (genetics, metabolism) Cell Differentiation (genetics) Cell Line Cell Transformation, Neoplastic (genetics, metabolism, pathology) DNA (metabolism) DNA-Binding Proteins (genetics, metabolism) Down-Regulation (genetics) Gene Expression Regulation HL-60 Cells HeLa Cells Homeodomain Proteins (genetics) Humans Leukemia (genetics, metabolism) Mice Mice, Inbred C57BL Models, Biological Myeloid Cells (cytology, metabolism) Myeloid Ecotropic Viral Integration Site 1 Protein Myeloid-Lymphoid Leukemia Protein (genetics, metabolism) Neoplasm Proteins (genetics) Nuclear Proteins (genetics, metabolism) Oncogene Proteins, Fusion (genetics, metabolism) Phosphoproteins (genetics, metabolism) Protein Binding (physiology) Protein Interaction Domains and Motifs (physiology) RNA Interference Recombinant Proteins (genetics, metabolism) Sequence Deletion (physiology) Transcription Factors (genetics, metabolism) Transcription, Genetic (physiology) Transcriptional Activation (genetics) Transfection Tumor Suppressor Proteins (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!