Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators.
The human thyroid hormone receptor-associated protein (TRAP) complex, an earlier described coactivator for nuclear receptors, and an SRB- and MED-containing cofactor complex (SMCC) that mediates activation by Gal4-p53 are shown to be virtually the same with respect to specific polypeptide subunits, coactivator functions, and mechanisms of action (activator interactions). In parallel with ligand-dependent interactions of nuclear receptors with the TRAP220 subunit, p53 and VP16 activation domains interact directly with a newly cloned TRAP80 subunit. These results indicate novel pathways for the function of nuclear receptors and other activators (p53 and VP16) through a common coactivator complex that is likely to target RNA polymerase II. Identification of the TRAP230 subunit as a previously predicted gene product also suggests a coactivator-related transcription defect in certain disease states.
Ito
M
M
Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, New York 10021, USA.
Yuan
C X
CX
Malik
S
S
Gu
W
W
Fondell
J D
JD
Yamamura
S
S
Fu
Z Y
ZY
Zhang
X
X
Qin
J
J
Roeder
R G
RG
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D003001:Cloning, Molecular; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D006801:Humans; D056892:Mediator Complex; D056913:Mediator Complex Subunit 1; D008969:Molecular Sequence Data; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D002352:Carrier Proteins; D005656:Fungal Proteins; D017405:Herpes Simplex Virus Protein Vmw65; C538855:MED1 protein, human; C492160:MED14 protein, human; C491485:MED6 protein, human; C538713:Med17 protein, human; D056892:Mediator Complex; D056913:Mediator Complex Subunit 1; D018167:Receptors, Calcitriol; D011988:Receptors, Thyroid Hormone; C074748:SRB2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D012319:RNA Polymerase II