title: Leucine-rich repeat-containing protein 59 mediates nuclear import of cancerous inhibitor of PP2A in prostate cancer cells.
abstract: Using yeast two-hybrid analysis, we identified several novel protein interactions for the oncoprotein Cancerous Inhibitor of PP2A (CIP2A) and confirmed a subset of these interactions in human cancer cell lines. Analysis of the interaction in prostate carcinoma cells between CIP2A and leucine-rich repeat-containing protein 59 (LRRC59) suggests that CIP2A is translocated into the nucleus at G2/M through its association with LRRC59. Recent work by others has demonstrated that nuclear CIP2A disrupts mitotic checkpoints, which promotes deregulation of the cell cycle and increases cancerous phenotypes. Thus, we provide a novel therapeutic mechanism for inhibiting CIP2A function in cancerous cells via targeting the CIP2A-LRRC59 interaction.
authors.affiliation: Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, Genesis Biotechnology Group, 1000 Waterview Drive, Hamilton, NJ, 08691, USA.
authors.forename: Rajash
authors.initials: R
authors.lastname: Pallai
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Bhaskar
authors.forename: Natalie
authors.initials: N
authors.lastname: Barnett-Bernodat
authors.forename: Christina
authors.initials: C
authors.lastname: Gallo-Ebert
authors.forename: Michelle
authors.initials: M
authors.lastname: Pusey
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Nickels
authors.forename: Lyndi M
authors.initials: LM
authors.lastname: Rice
mesh_terms: D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001324:Autoantigens; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; C574205:LRRC59 protein, human; D008565:Membrane Proteins; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2
references.citation: Cancer Med. 2015 Jun;4(6):903-13
references.pmid: 25663244
references.citation: Trends Mol Med. 2008 Apr;14(4):152-60
references.pmid: 18329957
references.citation: Cell Death Dis. 2014 Jul 31;5:e1359
references.pmid: 25077545
references.citation: IUBMB Life. 2010 Oct;62(10):724-31
references.pmid: 20979208
references.citation: Am J Pathol. 2014 Oct;184(10):2840-9
references.pmid: 25238935
references.citation: J Biol Chem. 2010 Sep 24;285(39):29863-73
references.pmid: 20663872
references.citation: PLoS One. 2013;8(2):e55705
references.pmid: 23383345
references.citation: J Biol Chem. 2014 Jan 3;289(1):28-40
references.pmid: 24214971
references.citation: Cancer Res. 2013 Nov 15;73(22):6667-78
references.pmid: 23983103
references.citation: Cancer Biol Ther. 2012 Mar;13(5):289-95
references.pmid: 22310977
references.citation: Mol Cancer Ther. 2014 Apr;13(4):938-47
references.pmid: 24448818
references.citation: Med Oncol. 2013;30(3):684
references.pmid: 23925667
references.citation: Cancer Res. 2009 Apr 1;69(7):2870-7
references.pmid: 19293187
references.citation: Traffic. 2012 May;13(5):650-64
references.pmid: 22321063
references.citation: Med Oncol. 2014 Aug;31(8):112
references.pmid: 25023053
references.citation: Biochem Pharmacol. 2013 Feb 1;85(3):356-66
references.pmid: 23178652
references.citation: Cancer Med. 2012 Aug;1(1):76-81
references.pmid: 23342256
references.citation: Clin Cancer Res. 2014 Apr 15;20(8):2092-103
references.pmid: 24436473
references.citation: Histopathology. 2013 Sep;63(3):438-9
references.pmid: 23802697
references.citation: Cell Cycle. 2008 Mar 1;7(5):592-6
references.pmid: 18256542
references.citation: Cancer Res. 2010 Dec 15;70(24):10474-84
references.pmid: 21159657
references.citation: Cell. 2007 Jul 13;130(1):21-4
references.pmid: 17632053
references.citation: Cancer Biol Ther. 2010 Oct 1;10(7):694-9
references.pmid: 21068540
references.citation: Biochim Biophys Acta. 2009 Jan;1795(1):1-15
references.pmid: 18588945
references.citation: Tumour Biol. 2015 Aug;36(8):6067-74
references.pmid: 25736928
references.citation: J Gastrointest Surg. 2012 May;16(5):1037-47
references.pmid: 22328001
references.citation: Br J Cancer. 2011 Sep 27;105(7):989-95
references.pmid: 21897396
references.citation: J Exp Clin Cancer Res. 2010 Oct 21;29:136
references.pmid: 20964854
references.citation: Front Physiol. 2012 Sep 18;3:355
references.pmid: 23060802
references.citation: PLoS One. 2012;7(3):e33209
references.pmid: 22461891
references.citation: Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):9157-62
references.pmid: 24927563
references.citation: Oral Oncol. 2012 Jul;48(7):585-93
references.pmid: 22342571
references.citation: Tumour Biol. 2012 Dec;33(6):2299-306
references.pmid: 22923389
references.citation: Cancer Res. 2014 Aug 15;74(16):4295-305
references.pmid: 24928782
references.citation: Neoplasia. 2012 Jul;14(7):585-99
references.pmid: 22904676
references.citation: Med Oncol. 2013 Jun;30(2):524
references.pmid: 23471718
references.citation: Cell. 2007 Jul 13;130(1):51-62
references.pmid: 17632056
references.citation: Oncogene. 2010 Nov 25;29(47):6257-66
references.pmid: 20729919
references.citation: PLoS One. 2011 Mar 22;6(3):e17979
references.pmid: 21445343
references.citation: Cancer Genomics Proteomics. 2012 Sep-Oct;9(5):265-73
references.pmid: 22990106
references.citation: Oncotarget. 2014 Jul 15;5(13):4581-602
references.pmid: 25015035
references.citation: Breast Cancer Res. 2012 Apr 26;14(2):R68
references.pmid: 22537901
references.citation: Cancer Res. 2013 Nov 15;73(22):6757-69
references.pmid: 24072747
references.citation: EMBO J. 2006 Feb 22;25(4):727-38
references.pmid: 16456541
references.citation: J Biol Chem. 2012 Mar 30;287(14):11030-6
references.pmid: 22315229
references.citation: Curr Top Med Chem. 2007;7(10):922-7
references.pmid: 17508923
references.citation: Tumour Biol. 2013 Aug;34(4):2309-13
references.pmid: 23568706
references.citation: Rheumatol Int. 2013 Sep;33(9):2241-8
references.pmid: 23455633
references.citation: Tumour Biol. 2015 Mar;36(3):1589-94
references.pmid: 25377160
references.citation: Clin Cancer Res. 2009 Aug 15;15(16):5092-100
references.pmid: 19671842
references.citation: Transcription. 2012 Nov-Dec;3(6):323-35
references.pmid: 23117818
references.citation: Mol Cell. 2011 Feb 18;41(4):471-9
references.pmid: 21329884
references.citation: Oncogene. 2011 Sep 1;30(35):3755-65
references.pmid: 21460856