PARTNER 1 – FORTH (IMBB)

Address:
Institute of Molecular Biology and Biotechnology,

P.O. Box 1527,

GR-711 10 Heraklion,

Greece.

Telephone: ++30-2810-1164

Fax: ++30-2810-391305

Email: mamalaki@imbb.forth.gr

Webpage: www.imbb.forth.gr

Members

Name	Email	Telephone
S. Papamatheakis	papamath@imbb.forth.gr	+30 2810 391165
K. Mamalaki	mamalaki@imbb.forth.gr	+30 2810 391164
G. Fousteri	fousteri@imbb.forth.gr	+30 2810 391174

Main Research Activities

Gene Expression in Mamalian Systems (S. Papamatheakis)

We study basic mechanisms that control gene expression. We have focused the last years on the molecular mechanisms that regulate the expression of the major histocompatibility complex (MHC) genes that have a central role in immunoregulation. MHC products are surface glycoproteins that control antigen presentation and the immune response. MHC gene expression is subject to developmental and cytokine-mediated regulation. The above, as well as genetic defects, target various regulatory components and affect MHC gene expression. We have used biochemical and cell systems to dissect and unravel the role of various regulatory components in MHC class II gene transcription.

Our contribution in understanding the mechanisms that control MHC expression includes the demonstration of important functional properties of the key transcriptional activator CIITA such as its interaction with general coactivators leading to their class II promoter targeting, its dimerization and acetylation which regulate its nuclear import-export properties. In parallel, the assembly of the class II enhanceosome was analysed in vitro using purified recombinant factors and in vivo using chromatin immunoprecipitation assays. This analysis allowed us to propose a dynamic model of gene regulation in this complex system (part A1).

Other activities aim at the development of novel chemicals that inhibit HAT activity (part A2), the elucidation of the biological functions of prothymosin A (part A3), the developmental regulation of the human transient axonal protein TAX1 expression (part A4) and molecular tools for gene immunotherapy (part A5).

Developmental and Functional Biology (K. Mamalaki)

Most Relevant Publications

1. Spilianakis, C., Papamatheakis, J. and Kretsovali, A. (2000). Acetylation by PCAF enhances CIITA nuclear accumulation and transactivation of MHC class II genes. Mol. Cell. Biol. 20:8489-8498.
2. Kretsovali, A., Spilianakis, C., Dimakopoulos, A., Makatounakis, T., Papamatheakis, J. (2001). Self-association of class II transactivator correlates with its intracellular localization and transactivation. J. Biol Chem. 276(34):32191-7.
3. Karetsou, Z., Kretsovali, A., Murphy, C., Tsolas, O., Papamarcaki, T. (2002) Prothymosin alpha interacts with the CREB-binding protein and potentiates transcription. EMBO Rep. 3(4):361-6.
4. Spilianakis,C., Agalioti, T., Kretsovali, A., Makatounakis, T., Thanos, D., Papamatheakis, J.. Interferon ?-induced transcription through CIITA-regulated cofactor recruitment and phosphorylation of RNAPII. (Submitted Mol. Cell)
5. Tzortzakaki, E., Spilianakis, C., Zika, E., Kretsovali, A., and Papamatheakis, J. Steroid receptor coactivator SRC-1 links the steroid and interferon ? response pathways (submitted JBC)
6. Denaxa, M., Pavlou, O., Tsiotra, P., Papadopoulos, G., Liapaki, K., Theodorakis, K., Karagogeos, D. and Papamatheakis, J. The upstream regulatory region of the human homologue of the Neuronal cell Adhesion Molecule TAG1 contains elements driving Neural Specific Expression in vivo. (Submitted)
7. Gritzapis, A., Kretsovali, A., Mamalaki, A., Papamatheakis, J., Belimezi, M., Papamichael, M., and Baxevanis, C. In vivo and in vitro antitumor activities of mouse CTL engineered to express chimeric single chain fragments from an HER-2/neu mAb and the ? chain from the Fc(?) RIII (in preparation).