Suppression of cell-cycle progression by Jun dimerization protein-2 (JDP2) involves downregulation of cyclin-A2.
We report here a novel role for Jun dimerization protein-2 (JDP2) as a regulator of the progression of normal cells through the cell cycle. To determine the role of JDP2 in vivo, we generated Jdp2-knockout (Jdp2KO) mice by targeting exon-1 to disrupt the site of initiation of transcription. The epidermal thickening of skin from the Jdp2KO mice after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) proceeded more rapidly than that of control mice, and more proliferating cells were found at the epidermis. Fibroblasts derived from embryos of Jdp2KO mice proliferated faster and formed more colonies than fibroblasts from wild-type mice. JDP2 was recruited to the promoter of the gene for cyclin-A2 (ccna2) at the AP-1 site. Cells lacking Jdp2 had elevated levels of cyclin-A2 mRNA. Furthermore, reintroduction of JDP2 resulted in the repression of transcription of ccna2 and of cell-cycle progression. Thus, transcription of the gene for cyclin-A2 appears to be a direct target of JDP2 in the suppression of cell proliferation.
Pan
J
J
RIKEN BioResource Center, Ibaraki, Japan.
Nakade
K
K
Huang
Y-C
YC
Zhu
Z-W
ZW
Masuzaki
S
S
Hasegawa
H
H
Murata
T
T
Yoshiki
A
A
Yamaguchi
N
N
Lee
C-H
CH
Yang
W-C
WC
Tsai
E-M
EM
Obata
Y
Y
Yokoyama
K K
KK
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D056751:Cyclin A2 / Q000235:genetics* / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D015536:Down-Regulation; D004817:Epidermis / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D055786:Gene Knockout Techniques; D017930:Genes, Reporter / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D056751:Cyclin A2; D016213:Cyclins; C491386:Jundp2 protein, mouse; D012097:Repressor Proteins; D018844:Cyclin-Dependent Kinases
Cancer Res. 2007 Jun 1;67(11):5126-33
17545590
Nat Rev Cancer. 2009 Mar;9(3):153-66
19238148
Cell Death Differ. 2007 Aug;14(8):1398-405
17464331
J Biol Chem. 2009 Apr 17;284(16):10808-17
19233846
FEBS Lett. 2008 Apr 30;582(10):1537-41
18396163
Mol Cell Biol. 2002 Jul;22(13):4815-26
12052888
Nat Rev Cancer. 2009 Oct;9(10):738-48
19776743
FEBS Lett. 2001 Jan 26;489(1):34-41
11231009
Cancer Res. 1998 Nov 1;58(21):4832-9
9809987
Mol Cell Biol. 1997 Jun;17(6):3094-102
9154808
Cell. 2009 Jul 23;138(2):352-65
19592082
J Exp Med. 2003 Apr 21;197(8):1029-35
12707301
Mol Cancer. 2010 Mar 09;9:54
20214788
EMBO J. 1992 Mar;11(3):961-71
1312467
Cell Div. 2010 Jan 17;5:2
20180967
Development. 1996 Jan;122(1):53-64
8565853
Biochim Biophys Acta. 2005 Aug 15;1745(1):29-37
16026868
Virology. 2005 Jul 5;337(2):353-64
15913695
J Biol Chem. 2002 Oct 18;277(42):40043-54
12171923
Nucleic Acids Res. 2009 Apr;37(7):2194-203
19233874
Mol Vis. 2008 Mar 04;14:431-42
18334960
J Cell Biol. 1999 Oct 18;147(2):295-306
10525536
Oncogene. 2003 Apr 10;22(14):2151-9
12687017
Genes Dev. 1999 Jun 15;13(12):1501-12
10385618
Cell. 2009 May 1;137(3):413-31
19410540
Oncogene. 1995 Jul 20;11(2):211-9
7624138
J Biol Chem. 2004 Aug 20;279(34):35858-66
15159393
Oncogene. 2009 Jul 23;28(29):2654-66
19483727
Mol Cell Biol. 2001 May;21(9):3012-24
11287607
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11293-8
12151601
Nucleic Acids Res. 2008 Jun;36(11):3608-19
18463134
Nat Struct Mol Biol. 2006 Apr;13(4):331-8
16518400
Curr Biol. 1998 Oct 8;8(20):1121-4
9778531
J Biol Chem. 2004 Feb 13;279(7):5708-15
14627710
Nucleic Acids Res. 2009 Aug;37(14):4657-71
19502497
Oncogene. 2009 Aug 20;28(33):2925-39
19561645