hCLP46 regulates U937 cell proliferation via Notch signaling pathway

Journal Article · Fri Apr 29 00:00:00 EDT 2011 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2011.03.124· OSTI ID:22204901

Ma, Wenzhan; Du, Jie; Chu, Qiaoyun ^[1]; Wang, Youxin ^[2]; Liu, Lixin ^[1]; Song, Manshu ^[2]; Wang, Wei ^[1]

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1. College of Life Science, Graduate University of Chinese Academy of Sciences, Beijing 100049 (China)
2. School of Public Health and Family Medicine, Capital Medical University, Beijing 100069 (China)

Highlights: {yields} Knock down of hCLP46 by RNAi impairs mammalian Notch signaling. {yields} hCLP46 affects neither cell surface Notch1 expression nor ligand-receptor binding. {yields} Knock down of hCLP46 inhibits U937 cell-growth by up-regulation of CDKN1B. -- 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.

• OSTI ID: 22204901
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 408, Issue 1; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL PROLIFERATION
DROSOPHILA
ENDOPLASMIC RETICULUM
GENE REGULATION
GROWTH FACTORS
LEUKEMIA
LIGANDS
PHOSPHORYLATION
RECEPTORS
RNA
TEARING INSTABILITY