TY - JOUR
T1 - Transcription cofactors TRIM24, TRIM28, and TRIM33 associate to form regulatory complexes that suppress murine hepatocellular carcinoma
AU - Herquel, Benjamin
AU - Ouararhni, Khalid
AU - Khetchoumian, Konstantin
AU - Ignat, Mihaela
AU - Teletin, Marius
AU - Mark, Manuel
AU - Béchade, Guillaume
AU - Van Dorsselaer, Alain
AU - Sanglier-Cianférani, Sarah
AU - Hamiche, Ali
AU - Cammas, Florence
AU - Davidson, Irwin
AU - Losson, Régine
PY - 2011/5/17
Y1 - 2011/5/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79957738075&partnerID=8YFLogxK
U2 - 10.1073/pnas.1101544108
DO - 10.1073/pnas.1101544108
M3 - Article
C2 - 21531907
AN - SCOPUS:79957738075
SN - 0027-8424
VL - 108
SP - 8212
EP - 8217
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 20
ER -