Open AccessOverexpression of hCLP 46 enhances Notch activation and regulates cell proliferation in a cell type‐dependent manner
Author(s) -
Chu Q.,
Liu L.,
Wang W.
Publication year - 2013
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12037
Subject(s) - notch signaling pathway , hes1 , microbiology and biotechnology , cell growth , notch 1 , cell , notch proteins , chemistry , biology , signal transduction , biochemistry
Objectives Human CAP10‐like protein 46 kDa ( hCLP 46), also known as Poglut1, has been shown to be an essential regulator of Notch signalling. hCLP 46 is overexpressed in primary acute myelogenous leukaemia, T‐acute lymphoblastic leukaemia samples and other leukaemia cell lines. However, effects of hCLP 46 overexpression, up to now, have remained unknown. Materials and methods In this study, we established stable 293TRex cell lines inducibly overexpressing hCLP 46, and knocked down hCLP 6 with a specific small interfering RNA to explore function of the protein in Notch signalling and cell proliferation. Results hCLP 46 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 hCLP 46 inhibited proliferation of 293TRexs and was correlated with increases in cyclin dependent kinase inhibitors p21 and p27, whereas reduced hCLP 46 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, hCLP 46 enhanced Notch activation and inhibited 293TRex cell proliferation through CDKI signalling.