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Gene Review

PDLIM7  -  PDZ and LIM domain 7 (enigma)

Homo sapiens

Synonyms: ENIGMA, LIM mineralization protein, LMP, LMP1, LMP3, ...
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Disease relevance of PDLIM7

  • Thus, LMP is a transforming gene which is likely to account for many aspects of EBV induced cell transformations [1].
  • While transgenic mice expressing LMP in many tissues demonstrated poor viability, expression of LMP specifically in the epidermis induces a phenotype of hyperplastic dermatosis [2].
  • The epithelial hyperplastic phenotype caused by the LMP-encoding transgenes implies that the LMP plays a role in the acanthotic condition of the tongue epithelium in the human EBV- and HIV-associated syndrome oral hairy leukoplakia, as well as possibly predisposing the nasopharyngeal epithelium to carcinogenesis [2].
  • LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12 [3].
  • 61 pregnant women in whom confirmed rubella occurred from 5 weeks before to 6 weeks after the last menstrual period (LMP) were followed up prospectively [4].

Psychiatry related information on PDLIM7

  • Central coherence theory (Frith, U., 1989. Autism: Explaining the Enigma. Blackwell, Oxford.) is addressed by exploring linguistic processing in normally intelligent adults with either autism or Asperger syndrome, to test whether local coherence is impaired [5].
  • METHOD: In this study, pregnant mothers were identified by the criteria of normalities, such as: well-known LMP, regular menstrual cycles, no use of OCP for the last 3 months, no use of alcohol or cigarettes, no drug abuse, no history of diabetes or chronic HTN [6].

High impact information on PDLIM7

  • The BNLF-1 gene of Epstein-Barr virus (EBV) encodes the latent membrane protein (LMP), one of the putative oncogene products of the virus [2].
  • Concomitant with the expression of LMP in this tissue (and in the esophagus) is an induction of the expression of a hyperproliferative keratin, K6, at aberrant locations within the epidermis [2].
  • Epstein-Barr virus expresses a cytoplasmic and plasma membrane protein (LMP) in latently infected growth transformed lymphocytes [1].
  • In Rat-1 cells, LMP expression often led to loss of contact inhibition and anchorage-independent growth in soft agar [1].
  • Transfection of an immortalized, non-tumorigenic keratinocyte cell line (RHEK-1) with the LMP gene causes a striking morphological transformation: the originally flat, polygonal colonies change to bundles of spindle-shaped cells that form multilayer foci, and cytokeratin expression is down-regulated [7].

Chemical compound and disease context of PDLIM7

  • A distinct LMP-specific membrane and cytoplasmic staining was detected exclusively in Hodgkin and Reed-Sternberg cells in 18 patients (38%); EBV nuclear antigen 2 and gp350/250 immunoreactivity was absent in all instances [8].
  • We show that LMP expression can be up regulated by exposure to n-butyrate and by superinfection with the B95-8 (B virus)- and P3HR1 (P virus)-derived EBV strains [9].
  • METHODS: Maternal age-specific sensitivity and false-positive rates for Down syndrome were derived for the triple test (alpha-fetoprotein, hCG, and unconjugated estriol) using gestational age based on ultrasound dating and also time from the last menstrual period (LMP) [10].
  • In 47 of the 109 HL patients (43%), immunohistochemical analysis of their formalin-fixed, paraffin-embedded histologic samples revealed Epstein-Barr virus (EBV) by latent membrane protein (LMP) 1 [11].

Biological context of PDLIM7

  • The recently revised cDNA sequence of Enigma, the protein product of which binds to the insulin receptor and the tyrosine kinase receptor ret, now matches the nucleotide sequence of human LMP-1 (hLMP-1) [12].
  • The interaction between Enigma and skeletal beta-TM was specific for the PDZ domain of Enigma, was abolished by mutations in the PDZ domain, and required the PDZ-binding consensus sequence (Thr-Ser-Leu) at the extreme carboxyl terminus of skeletal beta-TM [13].
  • METHODS: The date of the first day of the last menstrual period (LMP) was used to estimate the phase of the menstrual cycle when the surgeries were done [14].
  • Luteal phase was defined as day 15-42 from LMP [14].
  • Follicular phase was defined as day 1-14 from LMP [14].

Anatomical context of PDLIM7

  • The association of Enigma with skeletal beta-TM suggests a role for Enigma as an adapter protein that directs LIM-binding proteins to actin filaments of muscle cells [13].
  • We show that Enigma is present at the Z line in skeletal muscle and that the PDZ domain of Enigma binds to a skeletal muscle target, the actin-binding protein tropomyosin (skeletal beta-TM) [13].
  • Here we address the question of the effect of LMP expression on epithelial cells [7].
  • Morphological transformation of human keratinocytes expressing the LMP gene of Epstein-Barr virus [7].
  • LMP expression in RS cells varied according to the histological subtype of HD (1/10 cases [10%] of lymphocyte predominance subtype, 16/50 cases [32%] of nodular sclerosis, 23/24 [96%] cases of mixed cellularity type) [15].

Associations of PDLIM7 with chemical compounds

  • This localization was mediated by association with Enigma via the Ret/ptc2 sequence containing tyrosine 586 [16].
  • Re: Enigma of fluorouracil and levamisole [17].
  • Although LMP is fully soluble in isotonic Triton X-100 buffer, only 50% of it is extracted from cells in this solution [18].
  • By contrast, overexpression of Enigma inhibited insulin-stimulated glucose transport and Glut 4 translocation without alterations in proximal insulin signaling [19].
  • Interleukin 6 concentrations were lower after consumption of the oleic acid diet than after consumption of the LMP, TFA, and STE diets [20].

Other interactions of PDLIM7

  • Differential interaction of Enigma protein with the two RET isoforms [21].
  • Here we report a study on a human Enigma protein hCLIM1, in particular [22].
  • Because actin rearrangement is important for insulin-induced glucose transporter 4 (Glut 4) translocation, we studied the potential involvement of Enigma in insulin-induced glucose transport in 3T3-L1 adipocytes [19].
  • These findings suggest new roles for the ALP/Enigma protein family that may lead to the understanding of their involvement in cardiomyopathy [23].

Analytical, diagnostic and therapeutic context of PDLIM7

  • Thirty-two of 47 (68%) cases contained EBV-specific DNA sequences as detected by PCR, all LMP-positive cases being in this category [8].
  • For this purpose, three different approaches were applied: polymerase chain reaction (PCR) for the presence of EBV-DNA, in situ hybridization (ISH) for EBV-encoded small nuclear RNAs (EBER), and immunohistology for EBV-encoded latent membrane protein (LMP) [24].
  • Our results show that viral burden in HD is not primarily related to active viral replication, but is associated with LMP gene expression [25].
  • Our ability to isolate CTL specific for LMP proteins from individuals with HD and the sensitivity of R-S cells for CTL-mediated lysis suggest that the pursuit of specific adoptive immunotherapy represents a viable strategy for the subset of HD patients with EBV+ tumors [26].
  • Vimentin (or a vimentin-associated protein) may be a transducer of an LMP transmembrane effect in lymphoproliferation [18].


  1. An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Wang, D., Liebowitz, D., Kieff, E. Cell (1985) [Pubmed]
  2. Expression of the BNLF-1 oncogene of Epstein-Barr virus in the skin of transgenic mice induces hyperplasia and aberrant expression of keratin 6. Wilson, J.B., Weinberg, W., Johnson, R., Yuspa, S., Levine, A.J. Cell (1990) [Pubmed]
  3. LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12. Rotem-Yehudar, R., Groettrup, M., Soza, A., Kloetzel, P.M., Ehrlich, R. J. Exp. Med. (1996) [Pubmed]
  4. Outcome of confirmed periconceptional maternal rubella. Enders, G., Nickerl-Pacher, U., Miller, E., Cradock-Watson, J.E. Lancet (1988) [Pubmed]
  5. A test of central coherence theory: linguistic processing in high-functioning adults with autism or Asperger syndrome: is local coherence impaired? Jolliffe, T., Baron-Cohen, S. Cognition. (1999) [Pubmed]
  6. Assessment of fetal weight based on ultrasonic femur length after the second trimester. Honarvar, M., Allahyari, M., Dehbashi, S. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. (2001) [Pubmed]
  7. Morphological transformation of human keratinocytes expressing the LMP gene of Epstein-Barr virus. Fåhraeus, R., Rymo, L., Rhim, J.S., Klein, G. Nature (1990) [Pubmed]
  8. Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells. Herbst, H., Dallenbach, F., Hummel, M., Niedobitek, G., Pileri, S., Müller-Lantzsch, N., Stein, H. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  9. Up regulation of the Epstein-Barr virus (EBV)-encoded membrane protein LMP in the Burkitt's lymphoma line Daudi after exposure to n-butyrate and after EBV superinfection. Contreras-Salazar, B., Ehlin-Henriksson, B., Klein, G., Masucci, M.G. J. Virol. (1990) [Pubmed]
  10. Cost-effectiveness of estimating gestational age by ultrasonography in Down syndrome screening. Benn, P.A., Rodis, J.F., Beazoglou, T. Obstetrics and gynecology. (1999) [Pubmed]
  11. Association between the Epstein-Barr virus and Hodgkin's lymphoma in the North-Eastern part of Hungary: effects on therapy and survival. Keresztes, K., Miltenyi, Z., Bessenyei, B., Beck, Z., Szollosi, Z., Nemes, Z., Olah, E., Illes, A. Acta Haematol. (2006) [Pubmed]
  12. Overexpressed LIM mineralization proteins do not require LIM domains to induce bone. Liu, Y., Hair, G.A., Boden, S.D., Viggeswarapu, M., Titus, L. J. Bone Miner. Res. (2002) [Pubmed]
  13. The PDZ domain of the LIM protein enigma binds to beta-tropomyosin. Guy, P.M., Kenny, D.A., Gill, G.N. Mol. Biol. Cell (1999) [Pubmed]
  14. Mastectomy and oophorectomy by menstrual cycle phase in women with operable breast cancer. Love, R.R., Duc, N.B., Dinh, N.V., Shen, T.Z., Havighurst, T.C., Allred, D.C., DeMets, D.L. J. Natl. Cancer Inst. (2002) [Pubmed]
  15. Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease. Pallesen, G., Hamilton-Dutoit, S.J., Rowe, M., Young, L.S. Lancet (1991) [Pubmed]
  16. Shc and Enigma are both required for mitogenic signaling by Ret/ptc2. Durick, K., Gill, G.N., Taylor, S.S. Mol. Cell. Biol. (1998) [Pubmed]
  17. Re: Enigma of fluorouracil and levamisole. Healy, J.B. J. Natl. Cancer Inst. (1995) [Pubmed]
  18. An Epstein-Barr virus transforming protein associates with vimentin in lymphocytes. Liebowitz, D., Kopan, R., Fuchs, E., Sample, J., Kieff, E. Mol. Cell. Biol. (1987) [Pubmed]
  19. Enigma Interacts with Adaptor Protein with PH and SH2 Domains to Control Insulin-Induced Actin Cytoskeleton Remodeling and Glucose Transporter 4 Translocation. Barr??s, R., Gr??meaux, T., Gual, P., Gonzalez, T., Gugenheim, J., Tran, A., Le Marchand-Brustel, Y., Tanti, J.F. Mol. Endocrinol. (2006) [Pubmed]
  20. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets: a randomized crossover study. Baer, D.J., Judd, J.T., Clevidence, B.A., Tracy, R.P. Am. J. Clin. Nutr. (2004) [Pubmed]
  21. Differential interaction of Enigma protein with the two RET isoforms. Borrello, M.G., Mercalli, E., Perego, C., Degl'Innocenti, D., Ghizzoni, S., Arighi, E., Eroini, B., Rizzetti, M.G., Pierotti, M.A. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  22. Interaction of hCLIM1, an enigma family protein, with alpha-actinin 2. Kotaka, M., Kostin, S., Ngai, S., Chan, K., Lau, Y., Lee, S.M., Li, H., Ng, E.K., Schaper, J., Tsui, S.K., Fung, K., Lee, C., Waye, M.M. J. Cell. Biochem. (2000) [Pubmed]
  23. Molecular characterization of the Caenorhabditis elegans ALP/Enigma gene alp-1. McKeown, C.R., Han, H.F., Beckerle, M.C. Dev. Dyn. (2006) [Pubmed]
  24. Heterogeneous Epstein-Barr virus infection patterns in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type. Anagnostopoulos, I., Hummel, M., Finn, T., Tiemann, M., Korbjuhn, P., Dimmler, C., Gatter, K., Dallenbach, F., Parwaresch, M.R., Stein, H. Blood (1992) [Pubmed]
  25. Epstein-Barr virus burden in Hodgkin's disease is related to latent membrane protein gene expression but not to active viral replication. Joske, D.J., Emery-Goodman, A., Bachmann, E., Bachmann, F., Odermatt, B., Knecht, H. Blood (1992) [Pubmed]
  26. Isolation of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes that lyse Reed-Sternberg cells: implications for immune-mediated therapy of EBV+ Hodgkin's disease. Sing, A.P., Ambinder, R.F., Hong, D.J., Jensen, M., Batten, W., Petersdorf, E., Greenberg, P.D. Blood (1997) [Pubmed]
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