Open AccessGLTSCR 2 is an upstream negative regulator of nucleophosmin in cervical cancer
Author(s) -
Kim JeeYoun,
Cho YoungEun,
An YongMin,
Kim SangHoon,
Lee YongGwan,
Park JaeHoon,
Lee Sun
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12474
Subject(s) - nucleophosmin , ribosome biogenesis , nucleolus , nucleoplasm , microbiology and biotechnology , biology , regulator , subcellular localization , cell cycle , cytoplasm , ribosome , cell , cancer research , rna , genetics , gene , myeloid leukemia
Nucleophosmin ( NPM )/B23, a multifunctional nucleolar phosphoprotein, plays an important role in ribosome biogenesis, cell cycle regulation, apoptosis and cancer pathogenesis. The role of NPM in cells is determined by several factors, including total expression level, oligomerization or phosphorylation status, and subcellular localization. In the nucleolus, NPM participates in rRNA maturation to enhance ribosomal biogenesis. Consistent with this finding, NPM expression is increased in rapidly proliferating cells and many types of human cancers. In response to ribosomal stress, NPM is redistributed to the nucleoplasm, where it inactivates mouse double minute 2 homologue to stabilize p53 and inhibit cell cycle progression. These observations indicate that nucleolus‐nucleoplasmic mobilization of NPM is one of the key molecular mechanisms that determine the role of NPM within the cell. However, the regulatory molecule(s) that control(s) NPM stability and subcellular localization, crucial to the pluripotency of intercellular NPM , remain(s) unidentified. In this study, we showed that nucleolar protein GLTSCR 2/Pict‐1 induced nucleoplasmic translocation and enhanced the degradation of NPM via the proteasomal polyubiquitination pathway. In addition, we showed that GLTSCR 2 expression decreased the transforming activity of cells mediated by NPM and that the expression of NPM is reciprocally related to that of GLTSCR 2 in cervical cancer tissue. In this study, we demonstrated that GLTSCR 2 is an upstream negative regulator of NPM .