Transcription Cofactors TRIM24, TRIM28, and TRIM33 Associate to Form Regulatory Complexes That Suppress Murine Hepatocellular Carcinoma

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2011 May 3

PMID 21531907

Citations 111

Authors

Benjamin Herquel

Khalid Ouararhni

Konstantin Khetchoumian

Mihaela Ignat

Marius Teletin

Manuel Mark

Guillaume Bechade

Alain Van Dorsselaer

Sarah Sanglier-Cianferani

Ali Hamiche

Florence Cammas

Irwin Davidson

Regine Losson

Affiliations

Soon will be listed here.

Abstract

TRIM24 (TIF1α), TRIM28 (TIF1β), and TRIM33 (TIF1γ) are three related cofactors belonging to the tripartite motif superfamily that interact with distinct transcription factors. TRIM24 interacts with the liganded retinoic acid (RA) receptor to repress its transcriptional activity. Germ line inactivation of TRIM24 in mice deregulates RA-signaling in hepatocytes leading to the development of hepatocellular carcinoma (HCC). Here we show that TRIM24 can be purified as at least two macromolecular complexes comprising either TRIM33 or TRIM33 and TRIM28. Somatic hepatocyte-specific inactivation of TRIM24, TRIM28, or TRIM33 all promote HCC in a cell-autonomous manner in mice. Moreover, HCC formation upon TRIM24 inactivation is strongly potentiated by further loss of TRIM33. These results demonstrate that the TIF1-related subfamily of TRIM proteins interact both physically and functionally to modulate HCC formation in mice.

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References

Remboutsika E, Lutz Y, Gansmuller A, Vonesch J, Losson R, Chambon P . The putative nuclear receptor mediator TIF1alpha is tightly associated with euchromatin. J Cell Sci. 1999; 112 ( Pt 11):1671-83. DOI: 10.1242/jcs.112.11.1671. View

Bai X, Kim J, Yang Z, Jurynec M, Akie T, Lee J . TIF1gamma controls erythroid cell fate by regulating transcription elongation. Cell. 2010; 142(1):133-43. PMC: 3072682. DOI: 10.1016/j.cell.2010.05.028. View

Ignat M, Teletin M, Tisserand J, Khetchoumian K, Dennefeld C, Chambon P . Arterial calcifications and increased expression of vitamin D receptor targets in mice lacking TIF1alpha. Proc Natl Acad Sci U S A. 2008; 105(7):2598-603. PMC: 2268182. DOI: 10.1073/pnas.0712030105. View

Morsut L, Yan K, Enzo E, Aragona M, Soligo S, Wendling O . Negative control of Smad activity by ectodermin/Tif1gamma patterns the mammalian embryo. Development. 2010; 137(15):2571-8. DOI: 10.1242/dev.053801. View

Postic C, Magnuson M . DNA excision in liver by an albumin-Cre transgene occurs progressively with age. Genesis. 2000; 26(2):149-50. DOI: 10.1002/(sici)1526-968x(200002)26:2<149::aid-gene16>3.0.co;2-v. View

vom Baur E, Zechel C, Heery D, Heine M, Garnier J, Vivat V . Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1. EMBO J. 1996; 15(1):110-24. PMC: 449923. View

Rowe H, Jakobsson J, Mesnard D, Rougemont J, Reynard S, Aktas T . KAP1 controls endogenous retroviruses in embryonic stem cells. Nature. 2010; 463(7278):237-40. DOI: 10.1038/nature08674. View

Teyssier C, Ou C, Khetchoumian K, Losson R, Stallcup M . Transcriptional intermediary factor 1alpha mediates physical interaction and functional synergy between the coactivator-associated arginine methyltransferase 1 and glucocorticoid receptor-interacting protein 1 nuclear receptor coactivators. Mol Endocrinol. 2005; 20(6):1276-86. PMC: 1626528. DOI: 10.1210/me.2005-0393. View

Desmet V . East-West pathology agreement on precancerous liver lesions and early hepatocellular carcinoma. Hepatology. 2009; 49(2):355-7. DOI: 10.1002/hep.22681. View

10.

Cammas F, Mark M, Dolle P, Dierich A, Chambon P, Losson R . Mice lacking the transcriptional corepressor TIF1beta are defective in early postimplantation development. Development. 2000; 127(13):2955-63. DOI: 10.1242/dev.127.13.2955. View

11.

Beckstead R, Ortiz J, Sanchez C, Prokopenko S, Chambon P, Losson R . Bonus, a Drosophila homolog of TIF1 proteins, interacts with nuclear receptors and can inhibit betaFTZ-F1-dependent transcription. Mol Cell. 2001; 7(4):753-65. PMC: 3800173. DOI: 10.1016/s1097-2765(01)00220-9. View

12.

Miki T, Fleming T, Crescenzi M, Molloy C, Blam S, Reynolds S . Development of a highly efficient expression cDNA cloning system: application to oncogene isolation. Proc Natl Acad Sci U S A. 1991; 88(12):5167-71. PMC: 51833. DOI: 10.1073/pnas.88.12.5167. View

13.

Peng H, Feldman I, Rauscher 3rd F . Hetero-oligomerization among the TIF family of RBCC/TRIM domain-containing nuclear cofactors: a potential mechanism for regulating the switch between coactivation and corepression. J Mol Biol. 2002; 320(3):629-44. DOI: 10.1016/S0022-2836(02)00477-1. View

14.

Khetchoumian K, Teletin M, Tisserand J, Herquel B, Ouararhni K, Losson R . Trim24 (Tif1 alpha): an essential 'brake' for retinoic acid-induced transcription to prevent liver cancer. Cell Cycle. 2008; 7(23):3647-52. DOI: 10.4161/cc.7.23.7123. View

15.

Peng H, Begg G, Schultz D, Friedman J, Jensen D, Speicher D . Reconstitution of the KRAB-KAP-1 repressor complex: a model system for defining the molecular anatomy of RING-B box-coiled-coil domain-mediated protein-protein interactions. J Mol Biol. 2000; 295(5):1139-62. DOI: 10.1006/jmbi.1999.3402. View

16.

Schuler M, Dierich A, Chambon P, Metzger D . Efficient temporally controlled targeted somatic mutagenesis in hepatocytes of the mouse. Genesis. 2004; 39(3):167-72. DOI: 10.1002/gene.20039. View

17.

Kim J, Kaartinen V . Generation of mice with a conditional allele for Trim33. Genesis. 2008; 46(6):329-33. PMC: 2504017. DOI: 10.1002/dvg.20401. View

18.

Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M . FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination. Cell. 2009; 136(1):123-35. DOI: 10.1016/j.cell.2008.10.051. View

19.

Tsai W, Wang Z, Yiu T, Akdemir K, Xia W, Winter S . TRIM24 links a non-canonical histone signature to breast cancer. Nature. 2010; 468(7326):927-32. PMC: 3058826. DOI: 10.1038/nature09542. View

20.

Ouararhni K, Hadj-Slimane R, Ait-Si-Ali S, Robin P, Mietton F, Harel-Bellan A . The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity. Genes Dev. 2006; 20(23):3324-36. PMC: 1686608. DOI: 10.1101/gad.396106. View