Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P23193 (transcription elongation factor)
 739 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Positive transcription elongation factor-b (P-TEFb) contains CDK9 and cyclin T(1). P-TEFb was affinity purified from a stably transfected cell line that expresses epitope-tagged CDK9, and proteins that appeared to be specifically bound were sequenced. In addition to CDK9, previously identified isoforms of cyclin T (including T(1), T(2A) and T(2B)), HSP90 and CDC37, this analysis identified a novel protein named MCEF. Cloning of its cognate cDNA revealed that MCEF is the newest member of the AF4 family of transcription factors involved in acute lymphoblastic leukemia. MCEF RNA was expressed in all human tissues examined, and antisera directed against recombinant MCEF specifically immunoprecipitated P-TEFb. Ectopic expression of MCEF did not activate HIV-1 replication, and tethering of MCEF to a promoter did not activate transcription.
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PMID:MCEF, the newest member of the AF4 family of transcription factors involved in leukemia, is a positive transcription elongation factor-b-associated protein. 1206 98

Expression of the AF4-MLL fusion protein in murine hematopoietic progenitor/stem cells results in the development of proB acute lymphoblastic leukemia. In this study, we affinity purified the AF4-MLL and AF4 protein complexes to elucidate their function. We observed that the AF4 complex consists of 11 binding partners and exhibits positive transcription elongation factor b (P-TEFb)-mediated activation of promoter-arrested RNA polymerase (pol) II in conjunction with several chromatin-modifying activities. In contrast, the AF4-MLL complex consists of at least 16 constituents including P-TEFb kinase, H3K4(me3) and H3K79(me3) histone methyltransferases (HMT), a protein arginine N-methyltransferase and a histone acetyltransferase. These findings suggest that the AF4-MLL protein disturbs the fine-tuned activation cycle of promoter-arrested RNA Pol II and causes altered histone methylation signatures. Thus, we propose that these two processes are key to trigger cellular reprogramming that leads to the onset of acute leukemia.
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PMID:The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures. 2103 Sep 82