title: Calcium-dependent inhibition of polo-like kinase 3 activity by CIB1 in breast cancer cells.
abstract: Members of the polo-like kinases (Plk1, Plk2, Plk3 and Plk4) are involved in the regulation of various stages of the cell cycle and have been implicated in cancer progression. Unlike its other family members, the expression of Plk3 remains steady during cell cycle progression, suggesting that its activity may be spatiotemporally regulated. However, the mechanism of regulation of Plk3 activity is not well understood. Here, we show that calcium- and integrin-binding protein 1 (CIB1), a Plk3 interacting protein, is widely expressed in various cancer cell lines. Expression of CIB1 mRNA as well as protein is increased in breast cancer tissue as compared to normal tissue. CIB1 constitutively interacts with Plk3 as determined by both in vitro and in vivo assays. This interaction of CIB1 with Plk3 is independent of intracellular Ca(2+). Furthermore, binding of CIB1 results in inhibition of Plk3 kinase activity both in vitro and in vivo. Interestingly, this inhibition of the Plk3 activity by CIB1 is Ca(2+)-dependent. Taken together, our results suggest that CIB1 is a regulatory subunit of Plk3 and it regulates Plk3 activity in a Ca(2+)-dependent manner. Furthermore, upregulation of CIB1 in cancer cells could thus inhibit Plk3 activity leading to abnormal cell cycle regulation in breast cancer cells. Thus, in addition to Plk3, CIB1 may be a potential biomarker and target for therapeutic intervention of breast cancer.
authors.affiliation: Delaware Cardiovascular Research Center, University of Delaware, Newark, DE 19716, USA. unaik@udel.edu
authors.forename: Meghna U
authors.initials: MU
authors.lastname: Naik
authors.forename: Ngoc T
authors.initials: NT
authors.lastname: Pham
authors.forename: Kristin
authors.initials: K
authors.lastname: Beebe
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.forename: Ulhas P
authors.initials: UP
authors.lastname: Naik
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation; D000097868:Polo-like Kinases
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D017346:Protein Serine-Threonine Kinases; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; C109198:CIB1 protein, human; C486256:PLK3 protein, human; D000097868:Polo-like Kinases
references.citation: J Biol Chem. 2001 Sep 28;276(39):36194-9
references.pmid: 11447225
references.citation: Mol Cancer Res. 2003 Mar;1(5):376-84
references.pmid: 12651910
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9301-6
references.pmid: 9689075
references.citation: Mol Cell Biol. 2002 May;22(10):3450-9
references.pmid: 11971976
references.citation: Comput Methods Programs Biomed. 2004 Jul;75(1):67-73
references.pmid: 15158049
references.citation: Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4882-6
references.pmid: 8099445
references.citation: Oncogene. 2005 Jan 10;24(2):267-76
references.pmid: 15640842
references.citation: Cell Signal. 2000 Jun;12(6):405-11
references.pmid: 11202906
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1847-52
references.pmid: 17264206
references.citation: Blood. 2003 Aug 15;102(4):1355-62
references.pmid: 12714504
references.citation: Oncogene. 2000 Oct 5;19(42):4832-9
references.pmid: 11039900
references.citation: Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1984-9
references.pmid: 11854496
references.citation: Biochem Biophys Res Commun. 1997 May 19;234(2):397-405
references.pmid: 9177283
references.citation: J Biol Chem. 1997 Feb 21;272(8):4651-4
references.pmid: 9030514
references.citation: EMBO J. 1999 Oct 15;18(20):5528-39
references.pmid: 10523297
references.citation: Cancer Res. 2008 Jun 1;68(11):4077-85
references.pmid: 18519666
references.citation: Oncogene. 2002 Sep 26;21(43):6633-40
references.pmid: 12242661
references.citation: J Cutan Pathol. 2002 Jul;29(6):354-8
references.pmid: 12135466
references.citation: J Biol Chem. 2010 Jan 1;285(1):483-92
references.pmid: 19854831
references.citation: Mol Cell Biol. 1992 Sep;12(9):4164-9
references.pmid: 1508211
references.citation: EMBO Rep. 2002 Apr;3(4):341-8
references.pmid: 11897663
references.citation: Biochem J. 1999 Sep 15;342 Pt 3:729-35
references.pmid: 10477286
references.citation: Biochemistry. 2007 Aug 21;46(33):9551-63
references.pmid: 17655330
references.citation: Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6388-92
references.pmid: 8022793
references.citation: Curr Opin Cell Biol. 1998 Dec;10(6):776-83
references.pmid: 9914175
references.citation: Oncogene. 2005 Jan 10;24(2):287-91
references.pmid: 15640844
references.citation: Cell. 2003 Oct 3;115(1):83-95
references.pmid: 14532005
references.citation: Cancer Res. 2000 Dec 15;60(24):6826-31
references.pmid: 11156373
references.citation: J Biol Chem. 1995 Apr 28;270(17):10351-7
references.pmid: 7730342
references.citation: J Biol Chem. 1997 Nov 7;272(45):28646-51
references.pmid: 9353331
references.citation: Nat Cell Biol. 2000 Sep;2(9):672-6
references.pmid: 10980711
references.citation: Int J Oncol. 2002 Jan;20(1):121-6
references.pmid: 11743651
references.citation: J Biol Chem. 2001 Nov 16;276(46):43305-12
references.pmid: 11551930
references.citation: Genes Dev. 1998 Dec 15;12(24):3777-87
references.pmid: 9869630
references.citation: J Biol Chem. 1996 Aug 9;271(32):19402-8
references.pmid: 8702627
references.citation: Mol Cell Biol. 2003 Aug;23(16):5556-71
references.pmid: 12897130
references.citation: Anticancer Res. 2004 Jan-Feb;24(1):259-63
references.pmid: 15015605
references.citation: Science. 2002 Apr 19;296(5567):550-3
references.pmid: 11910072