Autoregulation of NFATc1/A expression facilitates effector T cells to escape from rapid apoptosis.
Threshold levels of individual NFAT factors appear to be critical for apoptosis induction in effector T cells. In these cells, the short isoform A of NFATc1 is induced to high levels due to the autoregulation of the NFATc1 promoter P1 by NFATs. P1 is located within a CpG island in front of exon 1, represents a DNase I hypersensitive chromatin site, and harbors several sites for binding of inducible transcription factors, including a tandemly arranged NFAT site. A second promoter, P2, before exon 2, is not controlled by NFATs and directs synthesis of the longer NFATc1/B+C isoforms. Contrary to other NFATs, NFATc1/A is unable to promote apoptosis, suggesting that NFATc1/A enhances effector functions without promoting apoptosis of effector T cells.
Department of Molecular Pathology, Institute of Pathology, University of Wuerzburg, D97080 Wuerzburg, Germany.
Sergei
S
Chuvpilo
Eriks
E
Jankevics
Dimitri
D
Tyrsin
Askar
A
Akimzhanov
Denis
D
Moroz
Mithilesh Kumar
MK
Jha
Jan
J
Schulze-Luehrmann
Brigitte
B
Santner-Nanan
Elizaveta
E
Feoktistova
Thomas
T
König
Andris
A
Avots
Edgar
E
Schmitt
Friederike
F
Berberich-Siebelt
Anneliese
A
Schimpl
Edgar
E
Serfling
D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D003850:Deoxyribonuclease I / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006706:Homeostasis; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011061:Poly A / Q000378:metabolism; D011401:Promoter Regions, Genetic; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; C494005:Nfatc1 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D011061:Poly A; D003850:Deoxyribonuclease I