title: Overexpression of hCLP46 enhances Notch activation and regulates cell proliferation in a cell type-dependent manner.
abstract: OBJECTIVE
  Human CAP10-like protein 46 kDa (hCLP46), also known as Poglut1, has been shown to be an essential regulator of Notch signalling. hCLP46 is overexpressed in primary acute myelogenous leukaemia, T-acute lymphoblastic leukaemia samples and other leukaemia cell lines. However, effects of hCLP46 overexpression, up to now, have remained unknown.
  
  
  METHODS
  In this study, we established stable 293TRex cell lines inducibly overexpressing hCLP46, and knocked down hCLP6 with a specific small interfering RNA to explore function of the protein in Notch signalling and cell proliferation.
  
  
  RESULTS
  hCLP46 overexpression enhanced Notch1 activation in 293Trex cells in a ligand-dependent manner, with increased Notch signalling enhancing Hes1 expression. We further verified that overexpression of hCLP46 inhibited proliferation of 293TRexs and was correlated with increases in cyclin dependent kinase inhibitors p21 and p27, whereas reduced hCLP46 expression moderately increased cell proliferation. In addition, p21 and p27 protein levels were higher when Notch signalling was activated by EDTA treatment.
  
  
  CONCLUSIONS
  Taken together, hCLP46 enhanced Notch activation and inhibited 293TRex cell proliferation through CDKI signalling.
authors.affiliation: College of Life Sciences, University of Chinese Academy of Sciences, Beijing100049, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Chu
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: W
authors.initials: W
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis; D002460:Cell Line; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D005964:Glucosyltransferases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D051881:Receptor, Notch1 / Q000378:metabolism; D015398:Signal Transduction; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004492:Edetic Acid; D005964:Glucosyltransferases; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; C497761:NOTCH1 protein, human; C078493:HES1 protein, human; C510651:POGLUT1 protein, human