title: Transcription cofactors TRIM24, TRIM28, and TRIM33 associate to form regulatory complexes that suppress murine hepatocellular carcinoma.
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.
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, 67404 Illkirch Cédex, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Herquel
authors.forename: Khalid
authors.initials: K
authors.lastname: Ouararhni
authors.forename: Konstantin
authors.initials: K
authors.lastname: Khetchoumian
authors.forename: Mihaela
authors.initials: M
authors.lastname: Ignat
authors.forename: Marius
authors.initials: M
authors.lastname: Teletin
authors.forename: Manuel
authors.initials: M
authors.lastname: Mark
authors.forename: Guillaume
authors.initials: G
authors.lastname: Béchade
authors.forename: Alain
authors.initials: A
authors.lastname: Van Dorsselaer
authors.forename: Sarah
authors.initials: S
authors.lastname: Sanglier-Cianférani
authors.forename: Ali
authors.initials: A
authors.lastname: Hamiche
authors.forename: Florence
authors.initials: F
authors.lastname: Cammas
authors.forename: Irwin
authors.initials: I
authors.lastname: Davidson
authors.forename: Régine
authors.initials: R
authors.lastname: Losson
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D022781:Hepatocytes / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology; D051379:Mice; D046912:Multiprotein Complexes / Q000302:isolation & purification / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D014157:Transcription Factors; C491420:Trim33 protein, mouse; C093517:transcriptional intermediary factor 1; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28