Interaction of Dimeric S100B(ββ) with the Tumor Suppressor Protein p53: A Model for Ca2+-Dependent S100-Target Protein Interactions
The tumor suppressor protein p53 interacts with a number of proteins to mediate its pleiotropic effects (Giaccia and Kastan, 1998; Levine, 1997). The Ca2+-dependent interaction of p53 with members of the S100 calcium binding protein family is of particular interest since like p53, these dimeric proteins affect cell cycle progression and are overexpressed in numerous tumor cells (Donato, 1991, 1999; Heizman, 1999; Ilg, 1996; Kligman and Hilt, 1988; Schafer and Heizmann, 1996; Zimmer et al., 1995). For example, reactive gliomas have as much as 20 times more S100B (ββ) than in non-transforming cell lines (Donato, 1991). Increased levels of S100B (ββ) are also found in renal cell tumors and malignant mature T-cells (such as doubly negative CD4−/CD8− adult T-cells in leukemia patients). As is the case for S100B(ββ), a number of other S100 proteins are often upregulated in cancer (Kligman and Hilt, 1988). For example, S100A1, S100A6, and S100B(ββ) are elevated significantly in metastatic human mammary epithelial cells (Schafer and Heizmann, 1996), and increased levels of CAPL (S100A4) in transgenic mice induce metastatic mammary tumors (Barraclough, 1998; Sherbet and Lakshmi, 1998). In the case of S100A4, expression of antisense RNA to S100A4 suppresses metastatic potential for a high-metastatic Lewis lung carcinoma (Barraclough, 1998; Sherbet and Lakshmi, 1998). In addition, protein levels of S100B(ββ), S100L (S100A2), S100A4, and S100A6 correlate with malignant melanoma as detected by antibodies specific for each protein (McNutt, 1998).
KeywordsS100 Protein Dime Interface Dependent Interaction S100 Protein Family Target Protein Binding
Unable to display preview. Download preview PDF.
- Barber K.R. McClintock K.A. Jamieson G.A. R.V.W D. and Shaw G.S. 1999 Specificity and Zn enhancement of S100B binding epitope TRTK-12 J. Biol. Chem. 274 1502–1508.Google Scholar
- Carrier, F., Blake, M., Zimmer, D., Rustandi, R.R. and Weber, D.J., 1999, Abrogation of p53 transcriptional activity by the S100 calcium binding proteins: Possible implication in angiogenesis, Proc. of the AACR 40, 102.Google Scholar
- Chiarugi, V., Cinelli, M. and Magnelli, L., 1998, Acetylation and phosphorylation of the carboxy-terminal domain of p53: Regulative significance, Oncology Res. 10, 55–57.Google Scholar
- Garbuglia, M., Verzini, M., Rustandi, R.R., Osterloh, D., Weber, D.J., Gerke, V. and Donato, R., 1999, Role of the C-terminal extension in the interaction of S100A1 and GFAP, tubilin, S100A1-and S100B-inhibitory peptide, TRTK-12, and a peptide derived from p53, and the S100A1 inhibitory effect on GFAP polymerization, Biochem. Biophys. Res. Commun. 254, 36–41.PubMedCrossRefGoogle Scholar
- Groves, P., Finn, B.E., Kuznicki, J. and Forsen, S., 1998, A model for target protein binding to calcium-activated S100 dimers, FEBS Lett. All, 175–179.Google Scholar
- Selivanova, G., Iotsova, V., Okan, I., Fritsche, M., Strom, M., Groner, B., Grafstrom, R.C. and Wiman, K.G., 1999, Restoration of the growth suppression function of mutant p53 by a synthetic peptide derived from the p53 C-terminal domain, Nature Med. 3, 632–638.Google Scholar
- Yap, K.L., Ames, J.B., Swindells, M.B. and Ikura, M., 1999, Diversity of conformational states and changes within the EF-hand protein superfamily, Proteins: Struct. Fund. Genet. 15, 499–507.Google Scholar