title: hCLP46 regulates U937 cell proliferation via Notch signaling pathway.
abstract: Human CAP10-like protein 46 kDa (hCLP46) is the homolog of Rumi, which is the first identified protein O-glucosyltransferase that modifies Notch receptor in Drosophila. Dysregulation of hCLP46 occurs in many hematologic diseases, but the role of hCLP46 remains unclear. Knockdown of hCLP46 by RNA interference resulted in decreased protein levels of endogenous Notch1, Notch intracellular domain (NICD) and Notch target gene Hes-1, suggesting the impairment of the Notch signaling. However, neither cell surface Notch expression nor ligand binding activities were affected. In addition, down-regulated expression of hCLP46 inhibited the proliferation of U937 cells, which was correlated with increased cyclin-dependent kinase inhibitor (CDKI) CDKN1B (p27) and decreased phosphorylation of retinoblastoma (RB) protein. We showed that lack of hCLP46 results in impaired ligand induced Notch activation in mammalian cell, and hCLP46 regulates the proliferation of U937 cell through CDKI-RB signaling pathway, which may be important for the pathogenesis of leukemia.
authors: College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Wenzhan
authors: W
authors: Ma
authors: Jie
authors: J
authors: Du
authors: Qiaoyun
authors: Q
authors: Chu
authors: Youxin
authors: Y
authors: Wang
authors: Lixin
authors: L
authors: Liu
authors: Manshu
authors: M
authors: Song
authors: Wei
authors: W
authors: Wang
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005964:Glucosyltransferases; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D020298:U937 Cells
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016203:CDC2 Protein Kinase; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005964:Glucosyltransferases; D018398:Homeodomain Proteins; D011506:Proteins; D051881:Receptor, Notch1; D051880:Receptors, Notch; D016160:Retinoblastoma Protein; D000072056:Transcription Factor HES-1; C436291:CDKN1B protein, human; C497761:NOTCH1 protein, human; C078493:HES1 protein, human; C510651:POGLUT1 protein, human