title: Regulation of the hematopoietic cell kinase (HCK) by PML/RARα and PU.1 in acute promyelocytic leukemia.
abstract: This study investigates the dynamic regulation of human hematopoietic cell kinase (HCK) in acute promyelocytic leukemia (APL) and the underlying molecular mechanisms. First, the level of HCK in APL blasts was found lower than that in normal granulocytes and monocytes. Second, the HCK promoter was repressed by PML/RARα and this repression required PU.1. PU.1 was capable of transactivating the HCK promoter through a region encompassing three PU.1 motifs. Chromatin immunoprecipitation assays provided evidence that PU.1 and PML/RARα bound to the HCK promoter in vivo. Finally, we found an unequivocal increase of HCK expression upon treatment with all-trans retinoic acid.
authors: State Key Laboratory of Medical Genomics, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Ruijin Rd II, Shanghai 200025, China.
authors: Dandan
authors: D
authors: Zou
authors: Xianwen
authors: X
authors: Yang
authors: Yun
authors: Y
authors: Tan
authors: Ping
authors: P
authors: Wang
authors: Xuehua
authors: X
authors: Zhu
authors: Wentao
authors: W
authors: Yang
authors: Xiaohong
authors: X
authors: Jia
authors: Ji
authors: J
authors: Zhang
authors: Kankan
authors: K
authors: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051572:Proto-Oncogene Proteins c-hck / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D000970:Antineoplastic Agents; D008156:Luciferases; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D051572:Proto-Oncogene Proteins c-hck; D012333:RNA, Messenger; D015534:Trans-Activators; D014212:Tretinoin; D000099232:Proto-Oncogene Protein Spi-1; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C496631:HCK protein, human