Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598766 (leukemogenesis)
 4,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human leukemias with chromosomal band 11q23 aberrations that disrupt the MLL/HRX/ALL-1 gene portend poor prognosis. MLL associated leukemias account for the majority of infant leukemia, approximately 10% of adult de novo leukemia and approximately 33% of therapy related acute leukemia with a balanced chromosome translocation. The 500 kD MLL precursor is processed by Taspase1 to generate mature MLL(N320/C180), which orchestrates many aspects of biology such as embryogenesis, cell cycle, cell fate and stem cell maintenance. Leukemogenic MLL translocations fuse the common MLL N-terminus (approximately 1,400 aa) in frame with more than 60 translocation partner genes (TPGs). Recent studies on MLL and MLL leukemia have greatly advanced our knowledge concerning the normal function of MLL and its deregulation in leukemogenesis. Here, we summarize the critical biological and pathological activities of MLL and MLL fusions, and discuss available models and potential therapeutic targets of MLL associated leukemias.
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PMID:MLL fusions: pathways to leukemia. 1972 89

Disrupting protein glycosylation induces ER (endoplasmic reticulum) stress, resulting in the activation of UPR (unfolded protein response) pathways. A key function of the UPR is to restore ER homeostasis, but prolonged or unsolved ER stress can lead to apoptosis. MLL1 (Mixed Lineage Leukemia 1, also named ALL-1 or HRX), a histone H3K4 methyltransferase in mammals, plays important roles in leukemogenesis, transcriptional regulation, cell cycle and development. Here, we find that Mll1 deficiency enhances UPR and apoptosis induced by the glycosylation inhibitor TM (tunicamycin). The abnormal regulation of the UPR appears to be caused by a defect in protein glycosylation. Furthermore, Mll1 directly binds to the promoters of H6pd, Galnt12 and Ugp2, which regulates H3K4 trimethylation and the subsequent expression of these genes. The knockdown of H6pd, Galnt12 or Ugp2 enhances TM-induced apoptosis in Mll1(+/+)MEF cells, whereas the ectopic expression of these proteins inhibits TM-induced apoptosis in Mll1(-/-) MEF cells. Together, our data suggest that the maturation of glycoproteins in the ER is subject to regulation at the epigenetic level by a histone methyltransferase whose abnormality can lead to cancer and developmental defects.
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PMID:Histone H3K4 methyltransferase Mll1 regulates protein glycosylation and tunicamycin-induced apoptosis through transcriptional regulation. 2498 72


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