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PDLIM4  -  PDZ and LIM domain 4

Homo sapiens

Synonyms: LIM protein RIL, PDZ and LIM domain protein 4, RIL, Reversion-induced LIM protein
 
 
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Disease relevance of PDLIM4

  • PDLIM4 repression by hypermethylation as a potential biomarker for prostate cancer [1].
  • Recombinant interleukin-2 (RIL 2)-activated autologous peripheral blood lymphocytes (PBL) were infused directly into the renal arteries of 3 patients with renal cell carcinoma, and the in vivo distribution of the infused cells was investigated [2].
  • Intravenous administration of these cells with the concomitant administration of RIL 2 can eliminate established pulmonary and hepatic metastases in mice [3].
  • We have recently shown that the systemic injection of RIL 2 given alone or in conjunction with LAK cells can reduce the number of established pulmonary and hepatic micrometastases from a weakly immunogenic sarcoma in mice [4].
  • Purified recombinant human interleukin 2 (RIL 2) derived from E. coli containing the inserted gene encoding for IL 2 was administered to 20 patients with a variety of malignancies [5].
  • Restoring RIL expression in colon cancer cells by stable transfection resulted in reduced cell growth and clonogenicity and an approximately 2.0-fold increase in apoptosis following UV exposure [6].
 

High impact information on PDLIM4

  • PBL collected by leukopheresis from each patient were thus cultured for 10 days with RIL 2, labeled with 111In-oxine, and then infused directly into the renal artery of the affected kidney via a catheter [2].
  • Our data point to the presence of a double PDZ-binding interface on the RIL-LIM domain and suggest tyrosine phosphorylation as a regulatory mechanism for LIM-PDZ associations in the assembly of multiprotein complexes [7].
  • Immunohistochemistry on various mouse tissues revealed a submembranous colocalization of PTP-BL and RIL in epithelial cells [7].
  • Moreover, injections of LAK cells plus RIL 2 were highly effective in eliminating established 3 day metastases in the lung and liver (1-3) [8].
  • Thus there was no requirement for additional T lymphocytes of host origin for successful therapy with adoptively transferred LAK cells plus RIL 2 [8].
 

Biological context of PDLIM4

  • Our data provide evidence of transcriptional repression of the putative tumor suppressor gene PDLIM4 by hypermethylation [1].
  • The human RIL gene: mapping to human chromosome 5q31.1, genomic organization and alternative transcripts [9].
  • We also identified two putative transcription start points (tsp) and sequenced the 5'-flanking region of RIL to reveal potential binding sites for transcriptional factors [9].
  • The major transcript is identical with the RIL cDNA previously deposited in GenBank and contains seven exons distributed over 14.5 kb of genomic DNA with the two last 3'-exons coding a LIM domain [9].
  • One candidate gene, the reversion-induced LIM gene ( RIL), is a PDZ and LIM-domain-containing protein and has been localized within the cytokine cluster of chromosome 5 (5q31.1) [10].
 

Anatomical context of PDLIM4

 

Associations of PDLIM4 with chemical compounds

  • A model of PDZ2 with the RIL peptide reveals that the PDZ2 binding pocket is able to accommodate the bulkier side-chain of glutamic acid while maintaining crucial protein to peptide hydrogen bond interactions [13].
 

Other interactions of PDLIM4

  • The second LIM domain in TRIP6 is sufficient for a strong interaction with RIL [14].
  • RNA expression analysis revealed overlapping patterns of expression for TRIP6, RIL and PTP-BL, most notably in tissues of epithelial origin [14].
  • In addition, PDZ2 specifically binds the C termini of both human Fas/CD95 receptor and the RIL protein, despite RIL containing a non-canonical PDZ-interacting sequence of E-x-V [13].
  • Association of genetic variation of the RIL gene, encoding a PDZ-LIM domain protein and localized in 5q31.1, with low bone mineral density in adult Japanese women [10].
 

Analytical, diagnostic and therapeutic context of PDLIM4

  • PCR analysis indicated the presence of two alternative RIL transcripts in human fetal brain mRNA [9].
  • These findings provide a rationale for clinical trials of infusion of LAK cells with RIL 2 in the therapy of HM in humans [4].
  • However, when combined with the systemic administration of RIL 2, these T cell-depleted, non-lytic LAK cells remained as effective in reducing the number of established pulmonary metastases upon adoptive transfer as untreated or complement-treated lytic LAK cells.(ABSTRACT TRUNCATED AT 400 WORDS)[8]
  • Adoptive immunotherapy of murine hepatic metastases with lymphokine activated killer (LAK) cells and recombinant interleukin 2 (RIL 2) can mediate the regression of both immunogenic and nonimmunogenic sarcomas and an adenocarcinoma [4].
  • Two major protein bands were observed in SDS-PAGE and W.B. EIA assay in all positive RIL extracts [15].

References

  1. PDLIM4 repression by hypermethylation as a potential biomarker for prostate cancer. Vanaja, D.K., Ballman, K.V., Morlan, B.W., Cheville, J.C., Neumann, R.M., Lieber, M.M., Tindall, D.J., Young, C.Y. Clin. Cancer Res. (2006) [Pubmed]
  2. In vivo distribution of recombinant interleukin-2-activated autologous lymphocytes administered by intra-arterial infusion in patients with renal cell carcinoma. Morita, T., Yonese, Y., Minato, N. J. Natl. Cancer Inst. (1987) [Pubmed]
  3. Murine lymphokine-activated killer (LAK) cells: phenotypic characterization of the precursor and effector cells. Yang, J.C., Mulé, J.J., Rosenberg, S.A. J. Immunol. (1986) [Pubmed]
  4. Adoptive immunotherapy of murine hepatic metastases with lymphokine activated killer (LAK) cells and recombinant interleukin 2 (RIL 2) can mediate the regression of both immunogenic and nonimmunogenic sarcomas and an adenocarcinoma. Lafreniere, R., Rosenberg, S.A. J. Immunol. (1985) [Pubmed]
  5. In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2. Lotze, M.T., Matory, Y.L., Ettinghausen, S.E., Rayner, A.A., Sharrow, S.O., Seipp, C.A., Custer, M.C., Rosenberg, S.A. J. Immunol. (1985) [Pubmed]
  6. RIL, a LIM gene on 5q31, is silenced by methylation in cancer and sensitizes cancer cells to apoptosis. Boumber, Y.A., Kondo, Y., Chen, X., Shen, L., Gharibyan, V., Konishi, K., Estey, E., Kantarjian, H., Garcia-Manero, G., Issa, J.P. Cancer Res. (2007) [Pubmed]
  7. PDZ motifs in PTP-BL and RIL bind to internal protein segments in the LIM domain protein RIL. Cuppen, E., Gerrits, H., Pepers, B., Wieringa, B., Hendriks, W. Mol. Biol. Cell (1998) [Pubmed]
  8. The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo: direct correlation between reduction of established metastases and cytolytic activity of lymphokine-activated killer cells. Mulé, J.J., Yang, J., Shu, S., Rosenberg, S.A. J. Immunol. (1986) [Pubmed]
  9. The human RIL gene: mapping to human chromosome 5q31.1, genomic organization and alternative transcripts. Bashirova, A.A., Markelov, M.L., Shlykova, T.V., Levshenkova, E.V., Alibaeva, R.A., Frolova, E.I. Gene (1998) [Pubmed]
  10. Association of genetic variation of the RIL gene, encoding a PDZ-LIM domain protein and localized in 5q31.1, with low bone mineral density in adult Japanese women. Omasu, F., Ezura, Y., Kajita, M., Ishida, R., Kodaira, M., Yoshida, H., Suzuki, T., Hosoi, T., Inoue, S., Shiraki, M., Orimo, H., Emi, M. J. Hum. Genet. (2003) [Pubmed]
  11. The PDZ-LIM protein RIL modulates actin stress fiber turnover and enhances the association of alpha-actinin with F-actin. Vallenius, T., Scharm, B., Vesikansa, A., Luukko, K., Schäfer, R., Mäkelä, T.P. Exp. Cell Res. (2004) [Pubmed]
  12. Actin/alpha-actinin-dependent transport of AMPA receptors in dendritic spines: role of the PDZ-LIM protein RIL. Schulz, T.W., Nakagawa, T., Licznerski, P., Pawlak, V., Kolleker, A., Rozov, A., Kim, J., Dittgen, T., Köhr, G., Sheng, M., Seeburg, P.H., Osten, P. J. Neurosci. (2004) [Pubmed]
  13. Structure, dynamics and binding characteristics of the second PDZ domain of PTP-BL. Walma, T., Spronk, C.A., Tessari, M., Aelen, J., Schepens, J., Hendriks, W., Vuister, G.W. J. Mol. Biol. (2002) [Pubmed]
  14. The zyxin-related protein TRIP6 interacts with PDZ motifs in the adaptor protein RIL and the protein tyrosine phosphatase PTP-BL. Cuppen, E., van Ham, M., Wansink, D.G., de Leeuw, A., Wieringa, B., Hendriks, W. Eur. J. Cell Biol. (2000) [Pubmed]
  15. A cholera-coli related enterotoxin production by different Shigella species. Panigrahi, D., Nayak, N., Ganguly, N.K., Roy, P., Sehgal, R. Indian journal of pathology & microbiology. (1993) [Pubmed]
 
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