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Human DAL-1 in complex with TSLC1

PDB Code 3BIN Target Class Lipid signalling Target EPB41L3 Alias 4.1B, DAL-1, DAL1, EPB41L3, FLJ37633, KIAA0987 Disease Area/Function cancer Date Deposited Nov 30 2007 Authors Busam, R.D., Arrowsmith, C.H., Collins, R., Dahlgren, L.G., Edwards, A.M., Flodin, S., Flores, A., Graslund, S., Hammarstrom, M., Johansson, A., Johansson, I., Kallas, A., Karlberg, T., Kotenyova, T., Lehtio, L., Moche, M., Nilsson, M.E., Nordlund, P., Nyman, T., Sagemark, J., Svensson, L., Thorsell, A.G., Tresaugues, L., Van Den Berg, S., Weigelt, J., Welin, M., Berglund, H., Persson, C., Hallberg, B.M. Related Structure 2HE7

About this structure

DAL-1/4.1B is known to suppress growth in meningiomas and can be lost in about 60% of sporadic meningiomas as an early event in tumorigenesis; it is a critical growth regulator in the pathogenesis of neoplastic transformation. Loss of DAL-1/4.1B has also been observed at high frequency in non-small-cell lung carcinomas. The protein belongs to the protein 4.1 superfamily. The members of this family are characterized by an N-terminal FERM domain, which localizes to the plasma membrane and links membrane associated proteins with the cytoskeleton. DAL-1/4.1B has been shown to bind tumor suppressor in lung cancer-1 (TSLC1) and connect this protein to the actin cytoskeleton. It was recently shown that DAL-1/4.1B binds and inhibits the action of a protein arginine N-methyltransferases 3. Recent results suggest that protein methylation cooperates with DAL-1/4.1B associated caspase 8-specific activation to induce apoptosis in breast cancer cells.

This is a follow-up structure to 2HE7.

References

Sun CX, Robb VA, Gutmann DH. Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation. J Cell Sci. 2002 Nov 1;115(Pt 21):3991-4000.

Heller G, Fong KM, Girard L, Seidl S, End-Pfutzenreuter A, Lang G, Gazdar AF, Minna JD, Zielinski CC, Zochbauer-Muller S. Expression and methylation pattern of TSLC1 cascade genes in lung carcinomas. Oncogene. 2006 Feb 9;25(6):959-68.

Gutmann DH, Donahoe J, Perry A, Lemke N, Gorse K, Kittiniyom K, Rempel SA, Gutierrez JA, Newsham IF. Loss of DAL-1, a protein 4.1-related tumor suppressor, is an important early event in the pathogenesis of meningiomas. Hum Mol Genet. 2000 Jun 12;9(10):1495-500.

Singh V, Miranda TB, Jiang W, Frankel A, Roemer ME, Robb VA, Gutmann DH, Herschman HR, Clarke S, Newsham IF. DAL-1/4.1B tumor suppressor interacts with protein arginine N-methyltransferase 3 (PRMT3) and inhibits its ability to methylate substrates in vitro and in vivo. Oncogene. 2004 Oct 14;23(47):7761-71.

Jiang W, Newsham IF. The tumor suppressor DAL-1/4.1B and protein methylation cooperate in inducing apoptosis in MCF-7 breast cancer cells. Mol Cancer. 2006 Jan 18;5(1):4