Reference SummaryHerquel B, Proc Natl Acad Sci U S A 2011 May 17;108(20):8212-7

Title

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

Authors

Herquel B; Ouararhni K; Khetchoumian K; Ignat M; Teletin M; Mark M; Bechade G; Van Dorsselaer A; Sanglier-Cianferani S; Hamiche A; Cammas F; Davidson I; Losson R

Journal

Proc Natl Acad Sci U S A

Volume

108

Issue

20

Year

2011

Pages

8212-7

Abstract

TRIM24 (TIF1alpha), TRIM28 (TIF1beta), and TRIM33 (TIF1gamma) 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.

Links

J:172605 – Mouse Genome Informatics
21531907 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
STOCK Speer6-ps1Tg(Alb-cre)21Mgn/? Trim24tm1Los Liver hepatocellular adenoma Liver

30

129-Albtm1(cre/ERT2)Mtz Trim24tm1Los Liver hepatocellular adenoma
  • tamoxifen (For inducing expression from mutant alleles)
Liver

35.71

[not specified]-Trim24tm1.1Los Liver hepatocellular adenoma Liver

50

STOCK Trim24tm1Los Liver hepatocellular adenoma Liver

0

129-Trim24tm1Los Liver hepatocellular adenoma
  • tamoxifen (For inducing expression from mutant alleles)
Liver

0

STOCK Speer6-ps1Tg(Alb-cre)21Mgn/? Trim24tm1Los Liver hepatocellular carcinoma Liver

30

129-Albtm1(cre/ERT2)Mtz Trim24tm1Los Liver hepatocellular carcinoma
  • tamoxifen (For inducing expression from mutant alleles)
Liver

14.29

[not specified]-Trim24tm1.1Los Liver hepatocellular carcinoma Liver

30

STOCK Trim24tm1Los Liver hepatocellular carcinoma Liver

0

129-Trim24tm1Los Liver hepatocellular carcinoma
  • tamoxifen (For inducing expression from mutant alleles)
Liver

0

STOCK Speer6-ps1Tg(Alb-cre)21Mgn/? Trim24tm1Los Liver preneoplastic lesion Liver

70

129-Albtm1(cre/ERT2)Mtz Trim24tm1Los Liver preneoplastic lesion
  • tamoxifen (For inducing expression from mutant alleles)
Liver

50

[not specified]-Trim24tm1.1Los Liver preneoplastic lesion Liver

70

STOCK Trim24tm1Los Liver preneoplastic lesion Liver

0

129-Trim24tm1Los Liver preneoplastic lesion
  • tamoxifen (For inducing expression from mutant alleles)
Liver

0

STOCK Speer6-ps1Tg(Alb-cre)21Mgn/? Trim24tm1Los Liver tumor - unclassified Liver

70 - 82.61

129-Albtm1(cre/ERT2)Mtz Trim24tm1Los Liver tumor - unclassified
  • tamoxifen (For inducing expression from mutant alleles)
Liver

50

[not specified]-Trim24tm1.1Los Liver tumor - unclassified Liver

70

STOCK Trim24tm1Los Liver tumor - unclassified Liver

0

129-Trim24tm1Los Liver tumor - unclassified Liver

0

B6;DBA-Speer6-ps1Tg(Alb-cre)21Mgn/? Liver tumor - unclassified Liver

0

STOCK Speer6-ps1Tg(Alb-cre)21Mgn/? Trim28tm1Ipc Liver tumor - unclassified Liver

31.58

STOCK Speer6-ps1Tg(Alb-cre)21Mgn/? Trim24tm1Los Trim28tm1Ipc Liver tumor - unclassified Liver

38.89

STOCK Speer6-ps1Tg(Alb-cre)21Mgn/? Trim33tm1Los Liver tumor - unclassified Liver

33.33

STOCK Speer6-ps1Tg(Alb-cre)21Mgn/? Trim24tm1Los Trim33tm1Los Liver tumor - unclassified Liver

100