Transcription intermediary factor 1gamma decreases protein expression of the transcriptional cofactor, LIM-domain-binding 1.
LIM-domain-binding 1 (LDB1) is a cofactor that participates in formation of regulatory complexes involving transcription factors containing LIM domains as well as other factors. We have examined the ability of transcriptional intermediary factor 1gamma (TIF1gamma) to decrease LDB1 expression. An expression vector for TIF1gamma was found to decrease expression of LDB1. A mutation which disrupts the ubiquitin ligase activity of TIF1gamma was found to block the ability of TIF1gamma to decrease LDB1 expression. Proteasome inhibitors were also able to block TIF1gamma effects on LDB1. Immunoprecipitation studies provided evidence that LDB1 interacts with TIF1gamma in intact cells. Knockdown of TIF1gamma in zebrafish embryos led to increased expression of LDB1 providing evidence for a physiological role of TIF1gamma in regulating LDB1 expression. Reporter gene assays demonstrated that TIF1gamma can alter the activity of LIM-homeodomain transcription factor-responsive promoters. These studies are consistent with a model in which TIF1gamma acts to ubiquitinate LDB1 leading to degradation of LDB1 and changes in transcription of LDB1-dependent promoters.
Howard
Paul W
PW
Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA.
Ransom
David G
DG
Maurer
Richard A
RA
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D047468:Immunoprecipitation; D060588:LIM Domain Proteins; D051379:Mice; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C486312:LDB1 protein, human; D060588:LIM Domain Proteins; C511956:TRIM33 protein, human; D014157:Transcription Factors
Development. 2000 May;127(9):1823-31
10751171
Cell. 2009 Jan 9;136(1):123-35
19135894
PLoS Biol. 2004 Aug;2(8):E237
15314655
Nature. 2002 Mar 7;416(6876):99-103
11882901
Cell. 2006 Jun 2;125(5):929-41
16751102
Cell. 2005 Apr 8;121(1):87-99
15820681
Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10403-8
10468620
Oncogene. 1999 Feb 4;18(5):1209-17
10022127
EMBO J. 1998 Dec 1;17(23):6846-53
9843490
Cell. 1994 Sep 9;78(5):773-85
8087845
Mol Cell Biol. 1994 May;14(5):2985-93
7513049
Mol Endocrinol. 1990 Apr;4(4):597-603
1704103
Bioessays. 2005 Nov;27(11):1147-57
16237670
Nature. 1996 Nov 21;384(6606):270-2
8918878
Development. 2003 Sep;130(17):4161-75
12874135
Mol Cell. 1999 Aug;4(2):267-73
10488342
Development. 2003 Feb;130(3):495-505
12490556
EMBO Rep. 2003 Dec;4(12):1132-7
14647207
EMBO J. 2000 Jun 1;19(11):2602-14
10835358
Genes Dev. 1998 Sep 15;12(18):2912-20
9744867
J Biol Chem. 1993 Feb 25;268(6):3903-10
7680035
J Biol Chem. 1999 Dec 17;274(51):36159-67
10593900
Mol Cell. 1999 Aug;4(2):259-65
10488341