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Third-party-funded project

Title:
The Control of the trancriptional Activity of NF-ATc in T Cells

Project management at the University of Würzburg:

• Prof. Dr. Edgar Serfling ,Tel: 201 474 31,Fax: 201 471 31,Mail: serfling.e@mail.uni-wuerzburg.de

Participating scientists:

• Dr. rer. nat. Andris Avots ,Tel: 201 474 95,Fax: 201 471 31,Mail: andy_avots@hotmail.com
• Dr. rer. nat. Sergei Chuvpilo ,Tel: 201 474 32,Fax: 201 471 31,Mail: chuvpilo@hotmail.com
• Dr. rer. nat. Alois Palmetshofer ,Tel: 201 471 00,Fax: 201 471 31,Mail: a.palmetshofer@mail.uni-wuerzburg.de
• Dipl. Biol. Jan Schulze-Luehrmann ,Tel: 201 474 95,Fax: 201 471 31,Mail: jan.schulze@mail.uni-wuerzburg.de
• Dipl.Biol. Denis Moroz ,Tel: 201 474 95,Fax: 201 471 31,Mail: mordv99@pisem.net
• Dipl. Biol. Askar Akimzhanov ,Tel: 201 474 95,Fax: 201 471 31,Mail: akimzhanov@hotmail.com
• Dipl.Biol. Dmitri Tyrsine ,Tel: 201 474 95,Fax: 201 471 31,Mail: Tyr@mail.ru

Abstract:
Activation of T lymphocytes results in a strong stimulation of expression of the NF-ATc gene and to high treshold-levels of NF-ATc/A, the short isoform of this transcription factor controlling the synthesis of numerous lymphokines. We cloned and characterized the exon/intron structure of the chromosomal NF-ATc gene spanning approx. 200 kB. Its expression is controled by two promoters, P1 and P2, and two poly A addition sites, pA1 and pA2. Whereas the inducible NF-ATc/A synthesis is controlled by P1 and pA1, the constitutive synthesis of longer NF-ATc isoforms B and C is controlled both by P1 and P2, and always by pA2. By binding to P1, NF-AT factors auto-regulate the expression of the NF-ATc gene.

Key words:
    NF-ATc gene
    promoter
    autoregulation

Projekt period: from 07.1999 to 12.2003

Funding institution:
DFG ( SFB 465 ) ,Granting date: 16.06.1999

Publications:

• Chuvpilo, S., Zimmer,M., Kerstan,A., Glöckner,J., Avots, A., Escher,C., Fischer,C., Iniashkina,I., Jankevics,E., Berberich-Siebelt,F., Schmitt,E., and Serfling,E.. (1999). Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells. Cell Press. 21. (monograph)
• Chuvpilo,S., Avots,A., Berberich-Siebelt,F., Glöckner,J., Fischer,C., Kerstan,A., Escher,C., Iniashkina,I., Hlubek,F., Jankevics,E., Brabletz,T.,and Serfling,E.. (1999). Multiple NF-ATc isoforms with individual transcriptional properties are synthesized in T lymphocytes. 7. (monograph)
• Chuvpilo,S., Jankevics,E., Tyrsin,D., Akimzhanov,A., Moroz,D., Jha,M.K., Schulze-Luehrmann,J., Santner-Nanan,B., Feoktistova,E., König,T., Avots,A., Schmitt,E., Berberich-Siebelt,F., Schimpl,A., and Serfling,E.. (2002). Autoregulation of NF-ATc1/A expression facilitates Effektor T cells to escape from rapid Apoptosis. Cell Press. 21. (monograph)