hCLP46 regulates U937 cell proliferation via Notch signaling pathway

Biochem Biophys Res Commun. 2011 Apr 29;408(1):84-8. doi: 10.1016/j.bbrc.2011.03.124. Epub 2011 Mar 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • CDC2 Protein Kinase / metabolism
  • Cell Proliferation*
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Gene Knockdown Techniques
  • Glucosyltransferases
  • Homeodomain Proteins / metabolism
  • Humans
  • Jurkat Cells
  • Leukemia / genetics
  • Leukemia / metabolism
  • Leukemia / pathology
  • Proteins / genetics
  • Proteins / physiology*
  • RNA Interference
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Retinoblastoma Protein / metabolism
  • Signal Transduction
  • Transcription Factor HES-1
  • U937 Cells

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • CDKN1B protein, human
  • Homeodomain Proteins
  • NOTCH1 protein, human
  • Proteins
  • Receptor, Notch1
  • Receptors, Notch
  • Retinoblastoma Protein
  • Transcription Factor HES-1
  • Cyclin-Dependent Kinase Inhibitor p27
  • HES1 protein, human
  • Glucosyltransferases
  • POGLUT1 protein, human
  • CDC2 Protein Kinase