Role of prothymosin a in cancer development, apoptosis, and immune response.

Project leader: Professor A.B.Vartapetian
D.Sc., Prof. Head, Laboratory of Molecular Biology of the Gene
A.N.Belozersky Institute of Physico-Chemical Biology

Address:   A.N.Belozersky Institute of Physico-Chemical Biology
           and Center of Molecular Medicine
           Moscow State University, 119899 Moscow, Russia

Tel.:      (7)(095) 930-0085
Fax:       (7)(095) 939-3181
E-mail:    varta@genebee.msu.su

List of project participants:

	Vadim I. Agol, D.Sc., Prof.
	George A. Belov, Senior Research Scientist
	Alexey A. Bogdanov, D.Sc., Prof.
	Nina V. Chichkova, Ph.D., Senior Research Scientist
	Alexandra G. Evstafieva, Ph.D., Senior Research Scientist
	Ruben N. Karapetian, Graduate Student
	Yuri P. Rubtsov, Ph.D., Research Scientist
	Vitaly R. Shakulov, Graduate Student

Brief project description:
	Substantial evidence indicates that cell division and cell death, 
although seemingly opposing, are tightly linked. It is likely therefore that 
analysis of the factors involved both in cell division and in programmed cell 
death (apoptosis) will lead to unraveling of the mechanisms that ensure fine 
balance between these two processes and may well provide the basis for more 
rational cancer therapies. The goal of the project is to investigate the role 
of a proliferation-related nuclear protein prothymosin a in cancer development,
apoptosis, and activation of the immune system, to elucidate the mechanisms 
underlying prothymosin a involvement in cell division, and to evaluate the 
possibility of using prothymosin a derivatives to manipulate these processes.
	The following aspects are being studied:
(i) The mechanism(s) of prothymosin a functioning in cell proliferation.
(ii) Elucidation of a role of prothymosin a and its fragmentation in apoptosis.
(iii) Examination of the trafficking of prothymosin a and caspase-generated 
prothymosin a fragments.

Recent publications (2000):

1. Evstafieva, A. G., Belov, G. A., Kalkum, M., Chichkova, N. V., Bogdanov, A. A.,
Agol, V. I., and Vartapetian, A. B. (2000) Prothymosin alpha fragmentation in
apoptosis. FEBS Lett.467, 150-154.
2. Chichkova, N. V., Evstafieva, A. G., Lyakhov, I. G., Tsvetkov, A. S., Smirnova,
T. A., Karapetian, R. N., Karger, E. M., and Vartapetian, A. B. (2000) Divalent
metal cation binding properties of human prothymosin *. Eur. J. Biochem. 267,
4745-4752.
3. Shakulov, V. R., Vorobjev, I. A., Rubtsov, Y. P., Chichkova, N. V., and
Vartapetian, A. B. (2000) Interaction of yeast importin * with the NLS of
prothymosin * is insufficient to trigger nuclear uptake of cargos. Biochem.
Biophys. Res. Commun.274, 548-552.
4. Belov, G. A., Evstafieva, A. G., Rubtsov, Y. P., Vartapetian, A. B., and
Agol, V. I. (2000) Early alteration of nucleocytoplasmic traffic induced by
some RNA viruses. Virology 275, 244-248.