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Gene Review

TGFB1I1  -  transforming growth factor beta 1 induced...

Homo sapiens

Synonyms: ARA55, Androgen receptor coactivator 55 kDa protein, Androgen receptor-associated protein of 55 kDa, HIC-5, HIC5, ...
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Disease relevance of TGFB1I1


High impact information on TGFB1I1


Chemical compound and disease context of TGFB1I1


Biological context of TGFB1I1

  • Suppression of androgen receptor transactivation by Pyk2 via interaction and phosphorylation of the ARA55 coregulator [8].
  • Recently, we found that enforced expression of ARA55 inhibits transforming growth factor-beta-mediated up-regulation of Smad binding element-luciferase reporter activity in NRP-154 and NRP-152 rat prostate and LNCaP human prostate cell lines [9].
  • These results suggest that Hic-5/ARA55 is required for optimal GR-mediated gene expression possibly by providing a scaffold that organizes or stabilizes coactivator complexes at some hormone-responsive promoters [10].
  • Hydrogen peroxide-inducible clone-5 (Hic-5), belongs to the group III LIM domain protein family and contains four carboxyl-terminal LIM domains (LIM1-LIM4) [11].
  • The ability of Hic-5/ARA55 to shuttle between the nuclear and cytoplasmic compartments was revealed on inhibition of nuclear export with leptomycin B [12].

Anatomical context of TGFB1I1

  • LIM4 also functions as a nuclear matrix targeting sequence (NMTS) for Hic-5/ARA55, as it is both necessary and sufficient to target a heterologous protein to the nuclear matrix [11].
  • Furthermore, a prostate stromal cell line, WPMY-1 cells, expresses Hic-5/ARA55, which is localized both at focal adhesion complexes and within the soluble cytoplasmic compartment [12].
  • Hic-5/ARA55, a LIM domain-containing nuclear receptor coactivator expressed in prostate stromal cells [12].
  • Hydrogen peroxide-inducible clone (Hic)-5 is induced during the senescent process in human fibroblasts, and the overexpression of Hic-5 induces a senescence-like phenotype [13].
  • However, Hic-5 is not tyrosine phosphorylated either by the coexpressed FAK in COS cells or by integrin stimulation in 293T cells [13].

Associations of TGFB1I1 with chemical compounds


Physical interactions of TGFB1I1


Co-localisations of TGFB1I1

  • In human embryonic kidney 293 cells, Hic-5 colocalizes with DAT at polarized sites and reduces DAT uptake activity through a mechanism involving a decrease in the cell-surface levels of the transporter [17].

Regulatory relationships of TGFB1I1

  • Moreover, ARA55 also inhibits the induction of Smad-binding element 4-luciferase and 3TP-luciferase (a plasminogen activator inhibitor-1 (PAI-1) promoter construct) reporters by constitutively active (CA)-Smad3 in these cell lines [9].

Other interactions of TGFB1I1


Analytical, diagnostic and therapeutic context of TGFB1I1


  1. Cloning and characterization of androgen receptor coactivator, ARA55, in human prostate. Fujimoto, N., Yeh, S., Kang, H.Y., Inui, S., Chang, H.C., Mizokami, A., Chang, C. J. Biol. Chem. (1999) [Pubmed]
  2. Modulation of androgen receptor transcriptional activity by anti-acne reagents. Inui, S., Nakao, T., Itami, S. J. Dermatol. Sci. (2004) [Pubmed]
  3. Subcellular targeting of oxidants during endothelial cell migration. Wu, R.F., Xu, Y.C., Ma, Z., Nwariaku, F.E., Sarosi, G.A., Terada, L.S. J. Cell Biol. (2005) [Pubmed]
  4. Inactivation of androgen receptor coregulator ARA55 inhibits androgen receptor activity and agonist effect of antiandrogens in prostate cancer cells. Rahman, M.M., Miyamoto, H., Lardy, H., Chang, C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk. Oda, A., Ochs, H.D., Lasky, L.A., Spencer, S., Ozaki, K., Fujihara, M., Handa, M., Ikebuchi, K., Ikeda, H. Blood (2001) [Pubmed]
  6. Hic-5-reduced cell spreading on fibronectin: competitive effects between paxillin and Hic-5 through interaction with focal adhesion kinase. Nishiya, N., Tachibana, K., Shibanuma, M., Mashimo, J.I., Nose, K. Mol. Cell. Biol. (2001) [Pubmed]
  7. Functional analysis of androgen receptor N-terminal and ligand binding domain interacting coregulators in prostate cancer. Yeh, S., Sampson, E.R., Lee, D.K., Kim, E., Hsu, C.L., Chen, Y.L., Chang, H.C., Altuwaijri, S., Huang, K.E., Chang, C. J. Formos. Med. Assoc. (2000) [Pubmed]
  8. Suppression of androgen receptor transactivation by Pyk2 via interaction and phosphorylation of the ARA55 coregulator. Wang, X., Yang, Y., Guo, X., Sampson, E.R., Hsu, C.L., Tsai, M.Y., Yeh, S., Wu, G., Guo, Y., Chang, C. J. Biol. Chem. (2002) [Pubmed]
  9. Novel function of androgen receptor-associated protein 55/Hic-5 as a negative regulator of Smad3 signaling. Wang, H., Song, K., Sponseller, T.L., Danielpour, D. J. Biol. Chem. (2005) [Pubmed]
  10. Mechanism of action of Hic-5/androgen receptor activator 55, a LIM domain-containing nuclear receptor coactivator. Heitzer, M.D., DeFranco, D.B. Mol. Endocrinol. (2006) [Pubmed]
  11. Distinct LIM domains of Hic-5/ARA55 are required for nuclear matrix targeting and glucocorticoid receptor binding and coactivation. Guerrero-Santoro, J., Yang, L., Stallcup, M.R., DeFranco, D.B. J. Cell. Biochem. (2004) [Pubmed]
  12. Hic-5/ARA55, a LIM domain-containing nuclear receptor coactivator expressed in prostate stromal cells. Heitzer, M.D., DeFranco, D.B. Cancer Res. (2006) [Pubmed]
  13. Interaction of Hic-5, A senescence-related protein, with focal adhesion kinase. Fujita, H., Kamiguchi, K., Cho, D., Shibanuma, M., Morimoto, C., Tachibana, K. J. Biol. Chem. (1998) [Pubmed]
  14. Interaction of the tau2 transcriptional activation domain of glucocorticoid receptor with a novel steroid receptor coactivator, Hic-5, which localizes to both focal adhesions and the nuclear matrix. Yang, L., Guerrero, J., Hong, H., DeFranco, D.B., Stallcup, M.R. Mol. Biol. Cell (2000) [Pubmed]
  15. Involvement of Hic-5 in platelet activation: integrin alphaIIbbeta3-dependent tyrosine phosphorylation and association with proline-rich tyrosine kinase 2. Osada, M., Ohmori, T., Yatomi, Y., Satoh, K., Hosogaya, S., Ozaki, Y. Biochem. J. (2001) [Pubmed]
  16. By modulating androgen receptor coactivators, daidzein may act as a phytoandrogen. Chen, J.J., Chang, H.C. Prostate (2007) [Pubmed]
  17. The multiple LIM domain-containing adaptor protein Hic-5 synaptically colocalizes and interacts with the dopamine transporter. Carneiro, A.M., Ingram, S.L., Beaulieu, J.M., Sweeney, A., Amara, S.G., Thomas, S.M., Caron, M.G., Torres, G.E. J. Neurosci. (2002) [Pubmed]
  18. Expression of AR associated protein 55 (ARA55) and androgen receptor in prostate cancer. Miyoshi, Y., Ishiguro, H., Uemura, H., Fujinami, K., Miyamoto, H., Miyoshi, Y., Kitamura, H., Kubota, Y. Prostate (2003) [Pubmed]
  19. Molecular cloning of human Hic-5, a potential regulator involved in signal transduction and cellular senescence. Zhang, J., Zhang, L.X., Meltzer, P.S., Barrett, J.C., Trent, J.M. Mol. Carcinog. (2000) [Pubmed]
  20. Expression of the LIM proteins paxillin and Hic-5 in human tissues. Yuminamochi, T., Yatomi, Y., Osada, M., Ohmori, T., Ishii, Y., Nakazawa, K., Hosogaya, S., Ozaki, Y. J. Histochem. Cytochem. (2003) [Pubmed]
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