title: GLTSCR2 is an upstream negative regulator of nucleophosmin in cervical cancer.
abstract: 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 GLTSCR2/Pict-1 induced nucleoplasmic translocation and enhanced the degradation of NPM via the proteasomal polyubiquitination pathway. In addition, we showed that GLTSCR2 expression decreased the transforming activity of cells mediated by NPM and that the expression of NPM is reciprocally related to that of GLTSCR2 in cervical cancer tissue. In this study, we demonstrated that GLTSCR2 is an upstream negative regulator of NPM.
authors.affiliation: Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Jee-Youn
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Cho
authors.affiliation: Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: An
authors.affiliation: Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Yong-Gwan
authors.initials: YG
authors.lastname: Lee
authors.affiliation: Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Sun
authors.initials: S
authors.lastname: Lee
mesh_terms: D015153:Blotting, Western; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D021381:Protein Transport; D059748:Proteolysis; D034622:RNA Interference; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C500712:NOP53 protein, human; C000716967:NPM1 protein, human; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D000090243:Nucleophosmin; D046988:Proteasome Endopeptidase Complex
keywords: GLTSCR2; cervical cancer; nucleophosmin; nucleoplasmic translocation
references.citation: Biochim Biophys Acta. 1987 Jul 16;925(1):74-82
references.pmid: 3593769
references.citation: Pathol Res Pract. 2010 May 15;206(5):295-9
references.pmid: 20185249
references.citation: Cancer Res. 1992 Jun 15;52(12):3372-7
references.pmid: 1596895
references.citation: Science. 1994 Mar 4;263(5151):1281-4
references.pmid: 8122112
references.citation: J Biol Chem. 1995 Apr 21;270(16):9429-36
references.pmid: 7721868
references.citation: Biochim Biophys Acta. 1995 May 17;1262(1):37-42
references.pmid: 7772597
references.citation: Blood. 1996 Feb 1;87(3):882-6
references.pmid: 8562957
references.citation: Oncogene. 1996 Jan 18;12(2):265-75
references.pmid: 8570204
references.citation: J Pathol. 1996 Jan;178(1):48-52
references.pmid: 8778315
references.citation: J Soc Gynecol Investig. 1997 Nov-Dec;4(6):298-304
references.pmid: 9408885
references.citation: Protein Sci. 1999 Apr;8(4):905-12
references.pmid: 10211837
references.citation: Prostate. 1999 Jun 1;39(4):298-304
references.pmid: 10344220
references.citation: N Engl J Med. 2005 Jan 20;352(3):254-66
references.pmid: 15659725
references.citation: Mol Pathol. 2000 Aug;53(4):184-7
references.pmid: 11040940
references.citation: Mol Cell. 2003 Nov;12(5):1151-64
references.pmid: 14636574
references.citation: Mol Cell Biol. 2004 Feb;24(3):985-96
references.pmid: 14729947
references.citation: Oncogene. 2011 Jun 9;30(23):2595-609
references.pmid: 21278791
references.citation: Nat Med. 2011 Aug;17(8):944-51
references.pmid: 21804542
references.citation: Am J Pathol. 2011 Sep;179(3):1257-64
references.pmid: 21741933
references.citation: Cell Death Differ. 2012 Oct;19(10):1613-22
references.pmid: 22522597
references.citation: Cancer Cell. 2004 May;5(5):465-75
references.pmid: 15144954
references.citation: J Biol Chem. 2004 Oct 1;279(40):41275-9
references.pmid: 15310764
references.citation: Mol Cell Biol. 2005 Feb;25(4):1258-71
references.pmid: 15684379
references.citation: Cancer Biol Ther. 2005 Sep;4(9):918-23
references.pmid: 16103750
references.citation: Cell Cycle. 2006 Apr;5(7):686-90
references.pmid: 16627991
references.citation: J Biol Chem. 2006 Jul 7;281(27):18463-72
references.pmid: 16679321
references.citation: Mol Biol Cell. 2006 Nov;17(11):4888-95
references.pmid: 16971513
references.citation: J Mol Histol. 2006 Sep;37(5-7):239-51
references.pmid: 16855788
references.citation: Haematologica. 2007 Apr;92(4):519-32
references.pmid: 17488663
references.citation: Chang Gung Med J. 2007 Jul-Aug;30(4):285-93
references.pmid: 17939258
references.citation: Cell Death Differ. 2007 Nov;14(11):1872-9
references.pmid: 17657248
references.citation: Cancer Res. 2008 Mar 1;68(5):1398-406
references.pmid: 18316603
references.citation: Mol Cell Biol. 2008 May;28(10):3114-26
references.pmid: 18332108
references.citation: Oncogene. 2008 Jul 10;27(30):4210-20
references.pmid: 18345031
references.citation: Blood. 2008 Sep 15;112(6):2474-83
references.pmid: 18574026
references.citation: J Pathol. 2008 Oct;216(2):218-24
references.pmid: 18729076
references.citation: BMC Cancer. 2009;9:378
references.pmid: 19849863
references.citation: Cancer Res. 2010 Feb 15;70(4):1656-67
references.pmid: 20145123
references.citation: J Cell Biol. 1988 Nov;107(5):1629-42
references.pmid: 3141428