Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in embryonic development and thyroid hormone action.
The TRAP220 component of the TRAP/SMCC complex, a mammalian homologof the yeast Mediator that shows diverse coactivation functions, interacts directly with nuclear receptors. Ablation of the murine Trap220 gene revealed that null mutants die during an early gestational stage with heart failure and exhibit impaired neuronal development with extensive apoptosis. Primary embryonic fibroblasts derived from null mutants show an impaired cell cycle regulation and a prominent decrease of thyroid hormone receptor function that is restored by ectopic TRAP220 but no defect in activation by Gal4-RARalpha/RXRalpha, p53, or VP16. Moreover, haploinsufficient animals show growth retardation, pituitary hypothyroidism, and widely impaired transcription in certain organs. These results indicate that TRAP220 is essential for a wide range of physiological processes but also that it has gene- and activator-selective functions.
Ito
M
M
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10021, USA.
Yuan
C X
CX
Okano
H J
HJ
Darnell
R B
RB
Roeder
R G
RG
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D005347:Fibroblasts / Q000502:physiology; D005804:Genes, Lethal; D006330:Heart Defects, Congenital; D008099:Liver / Q000196:embryology; D008168:Lung / Q000196:embryology; D056913:Mediator Complex Subunit 1; D051379:Mice; D018345:Mice, Knockout; D009421:Nervous System Malformations; D010902:Pituitary Gland / Q000196:embryology* / Q000378:metabolism; D010920:Placenta / Q000196:embryology; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D013961:Thyroid Gland / Q000196:embryology* / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D002352:Carrier Proteins; C070633:Gal-VP16; C538856:Med1 protein, mouse; D056913:Mediator Complex Subunit 1; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53