The transcription factor YY1 is a substrate for Polo-like kinase 1 at the G2/M transition of the cell cycle.
Yin-Yang 1 (YY1) is an essential multifunctional zinc-finger protein. It has been shown over the past two decades to be a critical regulator of a vast array of biological processes, including development, cell proliferation and differentiation, DNA repair, and apoptosis. YY1 exerts its functions primarily as a transcription factor that can activate or repress gene expression, dependent on its spatial and temporal context. YY1 regulates a large number of genes involved in cell cycle transitions, many of which are oncogenes and tumor-suppressor genes. YY1 itself has been classified as an oncogene and was found to be upregulated in many cancer types. Unfortunately, our knowledge of what regulates YY1 is very minimal. Although YY1 has been shown to be a phosphoprotein, no kinase has ever been identified for the phosphorylation of YY1. Polo-like kinase 1 (Plk1) has emerged in the past few years as a major cell cycle regulator, particularly for cell division. Plk1 has been shown to play important roles in the G/M transition into mitosis and for the proper execution of cytokinesis, processes that YY1 has been shown to regulate also. Here, we present evidence that Plk1 directly phosphorylates YY1 in vitro and in vivo at threonine 39 in the activation domain. We show that this phosphorylation is cell cycle regulated and peaks at G2/M. This is the first report identifying a kinase for which YY1 is a substrate.
Department of Biomedical Sciences, Florida State University, Tallahassee, Florida, United States of America.
Raed
R
Rizkallah
Karen E
KE
Alexander
Ari
A
Kassardjian
Bernhard
B
Lüscher
Myra M
MM
Hurt
D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division; D016195:G2 Phase; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D013912:Threonine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D050986:YY1 Transcription Factor / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D013912:Threonine; D014157:Transcription Factors; D050986:YY1 Transcription Factor; D000097869:Polo-Like Kinase 1; C494698:YY1 protein, human
Biochem J. 1999 Apr 15;339 ( Pt 2):435-42
10191277
J Biol Chem. 2001 Mar 16;276(11):7932-6
11118439
Eur J Cell Biol. 2010 Oct;89(10):748-56
20573420
Oncogene. 2005 Jan 10;24(2):267-76
15640842
Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12165-70
15295102
J Biol Chem. 2007 Sep 14;282(37):27414-27423
17623655
Int J Oncol. 2009 May;34(5):1417-23
19360355
Mol Biol Cell. 2009 Nov;20(22):4766-76
19793915
Nat Rev Cancer. 2006 Apr;6(4):321-30
16557283
EMBO J. 2002 Nov 1;21(21):5775-86
12411495
J Biol Chem. 1995 Dec 15;270(50):30213-20
8530432
Cell Cycle. 2010 Feb 1;9(3):512-22
20081375
Cell Cycle. 2009 Sep 1;8(17):2697-702
19652546
EMBO Rep. 2002 Apr;3(4):341-8
11897663
Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2199-204
17287340
Nat Rev Mol Cell Biol. 2007 Nov;8(11):894-903
17912263
J Cell Biol. 1995 Jun;129(6):1617-28
7790358
Mol Cell Biol. 2006 May;26(9):3565-81
16611997
Nat Cell Biol. 2008 Sep;10(9):1076-82
19160488
Eur J Haematol. 2008 Aug;81(2):112-22
18410541
Eur J Cancer. 2006 Oct;42(15):2420-4
16962318
IUBMB Life. 2005 Oct;57(10):677-82
16223707
Mol Cell Proteomics. 2008 Sep;7(9):1598-608
18463090
Gene. 1994 Dec 15;150(2):259-66
7821790
Blood. 2003 Feb 1;101(3):1111-7
12393438
Nat Rev Drug Discov. 2010 Aug;9(8):643-60
20671765
Mol Cell Biol. 1995 Dec;15(12):7143-51
8524282
Cell Cycle. 2004 Feb;3(2):128-31
14712072
PLoS One. 2007 May 02;2(5):e409
17476331
Science. 1993 Dec 17;262(5141):1889-92
8266081
Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5391-6
16565220
Int J Oncol. 2007 Jul;31(1):69-79
17549406
Biochem Biophys Res Commun. 2004 May 28;318(2):615-24
15120643
J Biol Chem. 1995 Sep 8;270(36):21086-91
7673138
Mol Cell Biol. 1998 Dec;18(12):7106-18
9819397
Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12130-5
15302935
Clin Cancer Res. 2009 Feb 1;15(3):851-7
19188155
Mol Biol Cell. 2002 Jun;13(6):1977-2000
12058064
J Cell Sci. 1998 Jun;111 ( Pt 12):1751-7
9601104
Am J Pathol. 2004 Mar;164(3):873-81
14982841
J Biol Chem. 1997 Apr 4;272(14):9166-74
9083047
EMBO J. 2007 May 2;26(9):2262-73
17446864
Biochim Biophys Acta. 1997 Apr 18;1332(2):F49-66
9141463
Cell Cycle. 2009 May;8(9):1305
19377298
J Biol Chem. 2003 Sep 19;278(38):35979-87
12815053
Cell Cycle. 2008 Nov 15;7(22):3556-63
19001871
Oncogene. 2005 Apr 18;24(17):2844-59
15838519
Neoplasia. 2004 Nov-Dec;6(6):744-50
15720800
Cancer Invest. 2009 Feb;27(2):184-92
19235591
Cancer Res. 2010 Feb 15;70(4):1513-23
20145140
Nature. 2001 Mar 8;410(6825):215-20
11242082
Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10638-41
8855231
Mol Cell Biol. 1999 Oct;19(10):7237-44
10490658
Curr Opin Cell Biol. 2008 Dec;20(6):650-60
19000759
Dev Cell. 2003 Jul;5(1):113-25
12852856
Cell. 1991 Oct 18;67(2):377-88
1655281
J Biol Chem. 1997 Jan 17;272(3):1709-17
8999850
J Biol Chem. 2003 Jul 11;278(28):25277-80
12738781
Mol Cell Biol. 1993 Dec;13(12):7487-95
8246966
Mol Cell Biol. 1996 Oct;16(10):5933-45
8816507
Genes Cells. 2005 Jul;10(7):717-31
15966902
Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7
18669648
Nat Chem Biol. 2006 Nov;2(11):608-17
17028581
Dev Cell. 2008 May;14(5):646-59
18477449
Oncogene. 2006 Feb 9;25(6):827-37
16247472
J Hepatol. 2008 Aug;49(2):170-4
18538438
J Cell Sci. 1988 Jan;89 ( Pt 1):25-38
3417791
Int J Oncol. 2005 Jul;27(1):131-41
15942652
J Cell Sci. 2004 Jan 26;117(Pt 3):465-76
14702388
Cell. 2004 Jun 25;117(7):859-72
15210108
Oncogene. 2006 Feb 23;25(8):1125-42
16314846