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hCLP46 regulates U937 cell proliferation via Notch signaling pathway

Ma, Wenzhan, Du, Jie, Chu, Qiaoyun, Wang, Youxin, Liu, Lixin, Song, Manshu, Wang, Wei
Biochemical and biophysical research communications 2011 v.408 no.1 pp. 84-88
Drosophila, RNA interference, cell proliferation, cyclin-dependent kinase, genes, hematologic diseases, humans, leukemia, pathogenesis, phosphorylation, signal transduction
Human CAP10-like protein 46kDa (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.