Transcription cofactors TRIM24, TRIM28, and TRIM33 associate to form regulatory complexes that suppress murine hepatocellular carcinoma

Benjamin Herquel, Khalid Ouararhni, Konstantin Khetchoumian, Mihaela Ignat, Marius Teletin, Manuel Mark, Guillaume Béchade, Alain Van Dorsselaer, Sarah Sanglier-Cianférani, Ali Hamiche, Florence Cammas, Irwin Davidson, Régine Losson

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Abstract

TRIM24 (TIF1á), TRIM28 (TIF1â), 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.

Original languageEnglish
Pages (from-to)8212-8217
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number20
DOIs
Publication statusPublished - 17 May 2011
Externally publishedYes

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Cite this

Herquel, B., Ouararhni, K., Khetchoumian, K., Ignat, M., Teletin, M., Mark, M., Béchade, G., Van Dorsselaer, A., Sanglier-Cianférani, S., Hamiche, A., Cammas, F., Davidson, I., & Losson, R. (2011). Transcription cofactors TRIM24, TRIM28, and TRIM33 associate to form regulatory complexes that suppress murine hepatocellular carcinoma. Proceedings of the National Academy of Sciences of the United States of America, 108(20), 8212-8217. https://doi.org/10.1073/pnas.1101544108