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Gene Review

MED1  -  mediator complex subunit 1

Homo sapiens

Synonyms: ARC205, Activator-recruited cofactor 205 kDa component, CRSP1, CRSP200, DRIP205, ...
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Disease relevance of PPARBP


Psychiatry related information on PPARBP

  • This was achieved by coupling the fusogenic carboxy-terminal part of the beta-amyloid peptide (Abeta, amino acids 29-40), involved in Alzheimer's disease, to a positively charged peptide (PIP2-binding peptide, PBP) interacting specifically with a naturally occurring negatively charged phospholipid, phosphatidylinositol 4, 5-bisphosphate (PIP2) [6].

High impact information on PPARBP

  • These data indicate that TRAP220 acts, via the TRAP complex, as a PPAR gamma(2)-selective coactivator and, accordingly, that it is specific for one fibroblast differentiation pathway (adipogenesis) relative to another (myogenesis) [7].
  • Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis [7].
  • We also show that transcriptional activation mediated by nuclear hormone receptors requires TATA-binding protein (TBP)-associated factors (TAFs) as well as the multi-subunit cofactors ARC/CRSP [8].
  • The ARC complex consists of 16 or more subunits; some of these are novel gene products, whereas others are present in other multisubunit cofactors, such as CRSP, NAT and mammalian Mediator [9].
  • Remarkably, the current study shows that MED1/TRAP220 only exists in a TRAP/Mediator subpopulation (less then 20% of the total) that is greatly enriched in specific TRAP/Mediator subunits and is tightly associated with a near stoichiometeric level of RNA polymerase II [10].

Chemical compound and disease context of PPARBP


Biological context of PPARBP


Anatomical context of PPARBP

  • High levels of PBP expression were detected in approximately 50% of primary breast cancers and breast cancer cell lines by ribonuclease protection analysis, in situ hybridization, and immunoperoxidase staining [1].
  • Studies with extracts from TRAP220(-/-) fibroblasts reveal that these interactions depend on TRAP220, a TRAP/Mediator subunit previously shown to interact with ER and other nuclear receptors in a ligand-dependent manner [17].
  • The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion [18].
  • Tumor cytosols that contained low levels of both cyst proteins (less than 225 ng/mg GCDFP-15 and less than 750 ng/mg PBP) had a high incidence of grade 3 (35 of 46, 78%) or grade 2 (15 of 46, 33%) histologic findings and had a high incidence of receptor-negative specimens (27 of 52, 52%) [3].
  • Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor [19].

Associations of PPARBP with chemical compounds

  • Human TRAP/Mediator is a key coactivator for many transcription factors that act through direct interactions with distinct subunits, and MED1/TRAP220 is the main subunit target for various nuclear receptors [10].
  • Peroxisome proliferator-activated receptor binding protein (PBP), a nuclear receptor coactivator, interacts with estrogen receptor alpha (ERalpha) in the absence of estrogen [1].
  • Distinct roles of the steroid receptor coactivator 1 and of MED1 in retinoid-induced transcription and cellular differentiation [20].
  • In this report, we characterize the nuclear receptor binding features of DRIP205, a key subunit of the DRIP complex, that interacts directly with VDR and thyroid hormone receptor in response to ligand and anchors the other DRIP subunits to the nuclear receptor LBD [21].
  • In common with other nuclear receptor coactivators, DRIP205 interaction occurs through one of two LXXLL motifs and requires the receptor's AF-2 subdomain [21].

Physical interactions of PPARBP

  • Vitamin D-interacting protein 205 (DRIP205) is a mediator complex protein that anchors the complex to the estrogen receptor (ER) and other nuclear receptors (NRs) [11].
  • These results suggested that a TRAP220 complex play an important role as putative co-activator complexes in BRCA1-mediated tumor suppression [22].
  • In this study we demonstrate that DRIP205 binds FXR in a ligand-dependent manner in vitro and in vivo [23].
  • Short LXXLL-containing nuclear receptor (NR) box peptides from P160 coactivators competed much better for SRC1a binding to flERE.E(2)-ER than an NR box peptide from TRAP220 [24].

Regulatory relationships of PPARBP


Other interactions of PPARBP


Analytical, diagnostic and therapeutic context of PPARBP

  • Finally, chromatin immunoprecipitation assays show that TRAP220 is recruited to the androgen-responsive prostate-specific antigen gene promoter in vivo in ligand-stimulated LNCaP cells [30].
  • We then performed interaction studies in vivo (co-immunoprecipitation) and in vitro (glutathione S-transferase pull-down assays) and showed that BRCT directly interacted with TRAP220 [22].
  • Electron microscopy and three-dimensional single-particle reconstruction reveals a conformation for CTD-CRSP that is structurally distinct from unliganded CRSP or CRSP bound to SREBP-1a, but highly similar to CRSP bound to the VP16 activator [31].
  • The purification, using preparative isoelectric focusing and chromatography on heparin-Sepharose, yielded two additional peptides with antiheparin activity that were immunologically identical with PBP: low-affinity platelet factor 4 and beta-thromboglubulin [32].
  • By using a specific radioimmunoassay it was shown that 10(9) human platelets contain 2-3 microgram of PBP which can be released in response to specific stimulation [32].


  1. Amplification and overexpression of peroxisome proliferator-activated receptor binding protein (PBP/PPARBP) gene in breast cancer. Zhu, Y., Qi, C., Jain, S., Le Beau, M.M., Espinosa, R., Atkins, G.B., Lazar, M.A., Yeldandi, A.V., Rao, M.S., Reddy, J.K. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  2. Gender difference in the activity but not expression of estrogen receptors alpha and beta in human lung adenocarcinoma cells. Dougherty, S.M., Mazhawidza, W., Bohn, A.R., Robinson, K.A., Mattingly, K.A., Blankenship, K.A., Huff, M.O., McGregor, W.G., Klinge, C.M. Endocr. Relat. Cancer (2006) [Pubmed]
  3. Biochemical correlates of morphologic differentiation in human breast cancer. Silva, J.S., Cox, C.E., Wells, S.A., Paull, D., Dilley, W.G., McCarty, K.S., Fetter, B.F., Glaubitz, L.C., McCarty, K.S. Surgery (1982) [Pubmed]
  4. Myofibroblast matrix metalloproteinases activate the neutrophil chemoattractant CXCL7 from intestinal epithelial cells. Kruidenier, L., MacDonald, T.T., Collins, J.E., Pender, S.L., Sanderson, I.R. Gastroenterology (2006) [Pubmed]
  5. Genes for a beta-lactamase, a penicillin-binding protein and a transmembrane protein are clustered with the cephamycin biosynthetic genes in Nocardia lactamdurans. Coque, J.J., Liras, P., Martín, J.F. EMBO J. (1993) [Pubmed]
  6. Enhanced efficiency of a targeted fusogenic peptide. Decout, A., Labeur, C., Goethals, M., Brasseur, R., Vandekerckhove, J., Rosseneu, M. Biochim. Biophys. Acta (1998) [Pubmed]
  7. Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis. Ge, K., Guermah, M., Yuan, C.X., Ito, M., Wallberg, A.E., Spiegelman, B.M., Roeder, R.G. Nature (2002) [Pubmed]
  8. Selectivity of chromatin-remodelling cofactors for ligand-activated transcription. Lemon, B., Inouye, C., King, D.S., Tjian, R. Nature (2001) [Pubmed]
  9. Composite co-activator ARC mediates chromatin-directed transcriptional activation. Näär, A.M., Beaurang, P.A., Zhou, S., Abraham, S., Solomon, W., Tjian, R. Nature (1999) [Pubmed]
  10. MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription. Zhang, X., Krutchinsky, A., Fukuda, A., Chen, W., Yamamura, S., Chait, B.T., Roeder, R.G. Mol. Cell (2005) [Pubmed]
  11. Vitamin D-interacting protein 205 (DRIP205) coactivation of estrogen receptor alpha (ERalpha) involves multiple domains of both proteins. Wu, Q., Burghardt, R., Safe, S. J. Biol. Chem. (2004) [Pubmed]
  12. New mechanism for methicillin resistance in Staphylococcus aureus: clinical isolates that lack the PBP 2a gene and contain normal penicillin-binding proteins with modified penicillin-binding capacity. Tomasz, A., Drugeon, H.B., de Lencastre, H.M., Jabes, D., McDougall, L., Bille, J. Antimicrob. Agents Chemother. (1989) [Pubmed]
  13. Characterization of clinical isolates of beta-lactamase-negative, highly ampicillin-resistant Enterococcus faecalis. Cercenado, E., Vicente, M.F., Díaz, M.D., Sánchez-Carrillo, C., Sánchez-Rubiales, M. Antimicrob. Agents Chemother. (1996) [Pubmed]
  14. Altered PBP 2A and its role in the development of penicillin, cefotaxime, and ceftriaxone resistance in a clinical isolate of Streptococcus pneumoniae. Smith, A.M., Feldman, C., Massidda, O., McCarthy, K., Ndiweni, D., Klugman, K.P. Antimicrob. Agents Chemother. (2005) [Pubmed]
  15. The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1. Ryu, S., Zhou, S., Ladurner, A.G., Tjian, R. Nature (1999) [Pubmed]
  16. RB18A regulates p53-dependent apoptosis. Frade, R., Balbo, M., Barel, M. Oncogene (2002) [Pubmed]
  17. The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro. Kang, Y.K., Guermah, M., Yuan, C.X., Roeder, R.G. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  18. The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion. Yuan, C.X., Ito, M., Fondell, J.D., Fu, Z.Y., Roeder, R.G. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  19. Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor. Zhu, Y., Qi, C., Jain, S., Rao, M.S., Reddy, J.K. J. Biol. Chem. (1997) [Pubmed]
  20. Distinct roles of the steroid receptor coactivator 1 and of MED1 in retinoid-induced transcription and cellular differentiation. Flajollet, S., Lefebvre, B., Rachez, C., Lefebvre, P. J. Biol. Chem. (2006) [Pubmed]
  21. The DRIP complex and SRC-1/p160 coactivators share similar nuclear receptor binding determinants but constitute functionally distinct complexes. Rachez, C., Gamble, M., Chang, C.P., Atkins, G.B., Lazar, M.A., Freedman, L.P. Mol. Cell. Biol. (2000) [Pubmed]
  22. BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220. Wada, O., Oishi, H., Takada, I., Yanagisawa, J., Yano, T., Kato, S. Oncogene (2004) [Pubmed]
  23. Identification of DRIP205 as a coactivator for the Farnesoid X receptor. Pineda Torra, I., Freedman, L.P., Garabedian, M.J. J. Biol. Chem. (2004) [Pubmed]
  24. In Vitro Fluorescence Anisotropy Analysis of the Interaction of Full-length SRC1a with Estrogen Receptors {alpha} and beta Supports an Active Displacement Model for Coregulator Utilization. Wang, S., Zhang, C., Nordeen, S.K., Shapiro, D.J. J. Biol. Chem. (2007) [Pubmed]
  25. Activation of TRAP/mediator subunit TRAP220/Med1 is regulated by mitogen-activated protein kinase-dependent phosphorylation. Pandey, P.K., Udayakumar, T.S., Lin, X., Sharma, D., Shapiro, P.S., Fondell, J.D. Mol. Cell. Biol. (2005) [Pubmed]
  26. Differential recruitment of the mammalian mediator subunit TRAP220 by estrogen receptors ERalpha and ERbeta. Wärnmark, A., Almlöf, T., Leers, J., Gustafsson, J.A., Treuter, E. J. Biol. Chem. (2001) [Pubmed]
  27. DNA binding-independent induction of IkappaBalpha gene transcription by PPARalpha. Delerive, P., De Bosscher, K., Vanden Berghe, W., Fruchart, J.C., Haegeman, G., Staels, B. Mol. Endocrinol. (2002) [Pubmed]
  28. Ligand-dependent interactions of coactivators steroid receptor coactivator-1 and peroxisome proliferator-activated receptor binding protein with nuclear hormone receptors can be imaged in live cells and are required for transcription. Llopis, J., Westin, S., Ricote, M., Wang, Z., Cho, C.Y., Kurokawa, R., Mullen, T.M., Rose, D.W., Rosenfeld, M.G., Tsien, R.Y., Glass, C.K., Wang, J. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  29. RB18A enhances expression of mutant p53 protein in human cells. Lottin-Divoux, S., Barel, M., Frade, R. FEBS Lett. (2005) [Pubmed]
  30. A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression. Wang, Q., Sharma, D., Ren, Y., Fondell, J.D. J. Biol. Chem. (2002) [Pubmed]
  31. Human CRSP interacts with RNA polymerase II CTD and adopts a specific CTD-bound conformation. Näär, A.M., Taatjes, D.J., Zhai, W., Nogales, E., Tjian, R. Genes Dev. (2002) [Pubmed]
  32. Human platelet basic protein associated with antiheparin and mitogenic activities: purification and partial characterization. Paul, D., Niewiarowski, S., Varma, K.G., Rucinski, B., Rucker, S., Lange, E. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
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