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Gene Review

RARRES3  -  retinoic acid receptor responder...

Homo sapiens

Synonyms: HRAS-like suppressor 4, HRASLS4, HRSL4, PLA1/2-3, RAR-responsive protein TIG3, ...
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Disease relevance of RARRES3


High impact information on RARRES3

  • Although the expression and function of these introduced genetic elements were essentially the same, among four HDF, TIG-1 and TIG-3 were resistant to transformation [6].
  • Tazarotene treatment increases TIG3 expression in primary human keratinocytes and in vivo in psoriatic lesions [3].
  • TIG3 localizes to the membrane fraction, and TIG3-dependent differentiation is associated with increased type I transglutaminase activity [7].
  • Tazarotene-induced protein 3 (TIG3) is a recently discovered regulatory protein that is expressed in the suprabasal epidermis [7].
  • Markers of apoptosis, including caspases and poly(ADP-ribose) polymerase, are not activated by TIG3, and caspase inhibitors do not stop the TIG3-dependent reduction in cell viability [7].

Chemical compound and disease context of RARRES3


Biological context of RARRES3


Anatomical context of RARRES3


Associations of RARRES3 with chemical compounds

  • The RIG1 regulation was related to cellular retinoid sensitivity [4].
  • Induction of TIG3, a putative class II tumor suppressor gene, by retinoic acid in head and neck and lung carcinoma cells and its association with suppression of the transformed phenotype [11].
  • The pan-RAR antagonists AGN193109 and the RARalpha antagonist Ro 41-5253 blocked TIG3 induction by ATRA [11].
  • E2 (1 nM) treatment for two days suppressed RIG1 mRNA levels in MCF-7 WS8 and ZR-75-1 cells, but not in the ER- ZR-75-30 cells [12].
  • Cellular proteins of a normal human diploid fibroblast line (TIG-3) at various stages of replicative aging were resolved by horizontal isoelectric focusing on an immobilized pH gradient, followed by vertical sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) [13].

Regulatory relationships of RARRES3


Other interactions of RARRES3

  • Further mechanisms must interfere with TIG3 expression that are independent of MEK and partially include interferon-responsive components [14].
  • The electrophoretic mobility of 13 human diploid cell strains, TIG-1, TIG-2, TIG-3, TIG-7, WI-38, IMR-90, MRC-5, MRC-9, TIG-1H, TIG-1L, TIG-2M, TIG-2B, and TIG-3S, which were established from different tissues of human embryos, was studied at different passages [16].
  • Finally, transcripts of retinoid-responsive genes, including RARRES3, RI58, NN8-4AG and midkine, were variably expressed [17].
  • ATRA (1 microM; 48 h) increased TIG3 mRNA in 4/5 HNSCCs and 3/5 NSCLCs and RARbeta mRNA in some of the same cell lines, but also in cells that did not show TIG3 induction [11].
  • The expression of retinoic acid-induced gene 1 (RIG1), a class II tumor suppressor gene, is induced in cells treated with retinoids [18].

Analytical, diagnostic and therapeutic context of RARRES3


  1. RARRES1 expression is significantly related to tumour differentiation and staging in colorectal adenocarcinoma. Wu, C.C., Shyu, R.Y., Chou, J.M., Jao, S.W., Chao, P.C., Kang, J.C., Wu, S.T., Huang, S.L., Jiang, S.Y. Eur. J. Cancer (2006) [Pubmed]
  2. Decreased expression of type II tumor suppressor gene RARRES3 in tissues of hepatocellular carcinoma and cholangiocarcinoma. Jiang, S.Y., Chou, J.M., Leu, F.J., Hsu, Y.Y., Shih, Y.L., Yu, J.C., Lee, M.S., Shyu, R.Y. World J. Gastroenterol. (2005) [Pubmed]
  3. Identification and characterization of a retinoid-induced class II tumor suppressor/growth regulatory gene. DiSepio, D., Ghosn, C., Eckert, R.L., Deucher, A., Robinson, N., Duvic, M., Chandraratna, R.A., Nagpal, S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  4. Cloning and characterization of a novel retinoid-inducible gene 1(RIG1) deriving from human gastric cancer cells. Huang, S.L., Shyu, R.Y., Yeh, M.Y., Jiang, S.Y. Mol. Cell. Endocrinol. (2000) [Pubmed]
  5. The class II tumor-suppressor gene RARRES3 is expressed in B cell lymphocytic leukemias and down-regulated with disease progression. Casanova, B., de la Fuente, M.T., Garcia-Gila, M., Sanz, L., Silva, A., Garcia-Marco, J.A., Garcia-Pardo, A. Leukemia (2001) [Pubmed]
  6. Refractory nature of normal human diploid fibroblasts with respect to oncogene-mediated transformation. Akagi, T., Sasai, K., Hanafusa, H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  7. A novel tumor suppressor protein promotes keratinocyte terminal differentiation via activation of type I transglutaminase. Sturniolo, M.T., Dashti, S.R., Deucher, A., Rorke, E.A., Broome, A.M., Chandraratna, R.A., Keepers, T., Eckert, R.L. J. Biol. Chem. (2003) [Pubmed]
  8. Tazarotene-induced gene 3 is suppressed in basal cell carcinomas and reversed in vivo by tazarotene application. Duvic, M., Ni, X., Talpur, R., Herne, K., Schulz, C., Sui, D., Ward, S., Joseph, A., Hazarika, P. J. Invest. Dermatol. (2003) [Pubmed]
  9. The class II tumour suppressor gene RARRES3 maps to 11q12, not 11q23. Auer, R.L., Bertoni, F., Jones, C., Cotter, F.E. Leukemia (2002) [Pubmed]
  10. RARRES3 expression positively correlated to tumour differentiation in tissues of colorectal adenocarcinoma. Shyu, R.Y., Jiang, S.Y., Chou, J.M., Shih, Y.L., Lee, M.S., Yu, J.C., Chao, P.C., Hsu, Y.J., Jao, S.W. Br. J. Cancer (2003) [Pubmed]
  11. Induction of TIG3, a putative class II tumor suppressor gene, by retinoic acid in head and neck and lung carcinoma cells and its association with suppression of the transformed phenotype. Higuchi, E., Chandraratna, R.A., Hong, W.K., Lotan, R. Oncogene (2003) [Pubmed]
  12. Expression and regulation of retinoid-inducible gene 1 (RIG1) in breast cancer. Shyu, R.Y., Chang, S.C., Yu, J.C., Hsu, S.J., Chou, J.M., Lee, M.S., Jiang, S.Y. Anticancer Res. (2005) [Pubmed]
  13. TMIG-2DPAGE: a new concept of two-dimensional gel protein database for research on aging. Toda, T., Kaji, K., Kimura, N. Electrophoresis (1998) [Pubmed]
  14. Suppression of the TIG3 tumor suppressor gene in human ovarian carcinomas is mediated via mitogen-activated kinase-dependent and -independent mechanisms. Lotz, K., Kellner, T., Heitmann, M., Nazarenko, I., Noske, A., Malek, A., Gontarewicz, A., Schäfer, R., Sers, C. Int. J. Cancer (2005) [Pubmed]
  15. Increase in expression levels of interferon-inducible genes in senescent human diploid fibroblasts and in SV40-transformed human fibroblasts with extended lifespan. Tahara, H., Kamada, K., Sato, E., Tsuyama, N., Kim, J.K., Hara, E., Oda, K., Ide, T. Oncogene (1995) [Pubmed]
  16. Changes in the cell surface of human diploid fibroblasts during cellular aging. Yamamoto, K., Yamamoto, M. Mutat. Res. (1991) [Pubmed]
  17. Expression of retinoid-related genes in serum-free cultures of normal, immortalized and malignant human oral keratinocytes. Dressler, D., Sarang, Z., Szondy, Z., Engelhart, K., Grafström, R.C. Int. J. Oncol. (2002) [Pubmed]
  18. Identification and characterization of the retinoic acid response elements in the human RIG1 gene promoter. Jiang, S.Y., Wu, M.S., Chen, L.M., Hung, M.W., Lin, H.E., Chang, G.G., Chang, T.C. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  19. Expression of a retinoid-inducible tumor suppressor, Tazarotene-inducible gene-3, is decreased in psoriasis and skin cancer. Duvic, M., Helekar, B., Schulz, C., Cho, M., DiSepio, D., Hager, C., DiMao, D., Hazarika, P., Jackson, B., Breuer-McHam, J., Young, J., Clayman, G., Lippman, S.M., Chandraratna, R.A., Robinson, N.A., Deucher, A., Eckert, R.L., Nagpal, S. Clin. Cancer Res. (2000) [Pubmed]
  20. Telomerase activity reconstituted in vitro with purified human telomerase reverse transcriptase and human telomerase RNA component. Masutomi, K., Kaneko, S., Hayashi, N., Yamashita, T., Shirota, Y., Kobayashi, K., Murakami, S. J. Biol. Chem. (2000) [Pubmed]
  21. Telomerase rescues the expression levels of keratinocyte growth factor and insulin-like growth factor-II in senescent human fibroblasts. Kanzaki, Y., Onoue, F., Ishikawa, F., Ide, T. Exp. Cell Res. (2002) [Pubmed]
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