Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gene rearrangements generate MLL fusion genes, which can lead to aggressive leukemia. In most cases, MLL fuses with a gene encoding a component of the AEP (AF4 family/ENL family/P-TEFb) coactivator complex. MLL-AEP fusion proteins constitutively activate their target genes to immortalize haematopoietic progenitors. Here we show that AEP and MLL-AEP fusion proteins activate transcription through selectivity factor 1 (SL1), a core component of the pre-initiation complex (PIC) of RNA polymerase I (RNAP1). The pSER domain of AF4 family proteins associates with SL1 on chromatin and loads TATA-binding protein (TBP) onto the promoter to initiate RNA polymerase II (RNAP2)-dependent transcription. These results reveal a previously unknown transcription initiation mechanism involving AEP and a role for SL1 as a TBP-loading factor in RNAP2-dependent gene activation.
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PMID:AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription. 2659 43

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause aggressive leukemia. Fusion proteins of MLL and a component of the AF4 family/ENL family/P-TEFb complex (AEP) are responsible for two-thirds of MLL-associated leukemia cases. MLL-AEP fusion proteins trigger aberrant self-renewal of hematopoietic progenitors by constitutively activating self-renewal-related genes. MLL-AEP fusion proteins activate transcription initiation by loading the TATA-binding protein (TBP) to the TATA element via selectivity factor 1. Although AEP retains transcription elongation and mediator recruiting activities, the rate-limiting step activated by MLL-AEP fusion proteins appears to be the TBP-loading step. This is contrary to prevailing views, in which the recruitment of transcription elongation activities are emphasized. Here, I review recent advances towards elucidating the mechanisms underlying gene activation by MLL-AEP fusion proteins in leukemogenesis.
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PMID:Transcriptional activation by MLL fusion proteins in leukemogenesis. 2786 5