The Bcl-2 gene is differentially regulated by IL-2 and IL-4: role of the transcription factor NF-AT.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print Cited Medium: Print ISSN: 0950-9232 (Print) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE

Publication: <2002->: Basingstoke : Nature Publishing Group
Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-

Bacterial Proteins* ; Nuclear Proteins*; DNA-Binding Proteins/*metabolism ; Interleukin-2/*metabolism ; Interleukin-4/*metabolism ; Proto-Oncogene Proteins c-bcl-2/*genetics ; Transcription Factors/*metabolism; Androstadienes/pharmacology ; Animals ; Bacterial Toxins/pharmacology ; Calcineurin/metabolism ; Calcineurin Inhibitors ; Cell Line ; Cyclosporine/pharmacology ; DNA-Binding Proteins/genetics ; Down-Regulation ; Gene Expression Regulation ; Interleukin-2/genetics ; Interleukin-2/pharmacology ; Interleukin-4/genetics ; Interleukin-4/pharmacology ; Mice ; NFATC Transcription Factors ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Sp1 Transcription Factor/metabolism ; T-Lymphocytes/drug effects ; Tacrolimus/pharmacology ; Transcription Factor AP-1/metabolism ; Transcription Factors/genetics ; Transcriptional Activation ; Up-Regulation ; Wortmannin

The murine TS1alphabeta T cell line expresses the anti-apoptotic protein Bcl-2 upon IL-2 stimulation, whereas IL-4-mediated growth of this cell line proceeds in the absence of Bcl-2 expression. In addition, IL-4 stimulation inhibits Bcl-2 expression and modulates its mRNA level. IL-2-induced DNA binding activity for these transcription factors is sensitive to phosphatidylinositol 3 kinase inhibitor wortmannin and to Rho inhibitor Clostridium difficile toxin B, which inhibit IL-2-induced Bcl-2 expression. NF-AT transcription factor appears to be the most important in the control Bcl-2 expression, since inhibition of the calcium-calmodulin-dependent phosphatase calcineurin, which regulates NF-AT activity, downregulates Bcl-2 expression in IL-2-stimulated cells. Constitutive expression of this phosphatase also upregulates Bcl-2 expression in IL-4-stimulated cells. In addition, a dominant negative NF-AT expression vector downregulates Bcl-2 expression in IL-2-stimulated cells. These results suggest that IL-2 induction of Bcl-2 expression may be directly or indirectly mediated by NF-AT.

0 (Androstadienes)
0 (Bacterial Proteins)
0 (Bacterial Toxins)
0 (Calcineurin Inhibitors)
0 (DNA-Binding Proteins)
0 (Interleukin-2)
0 (NFATC Transcription Factors)
0 (Nuclear Proteins)
0 (Proto-Oncogene Proteins c-bcl-2)
0 (Sp1 Transcription Factor)
0 (Transcription Factor AP-1)
0 (Transcription Factors)
0 (toxB protein, Clostridium difficile)
207137-56-2 (Interleukin-4)
83HN0GTJ6D (Cyclosporine)
EC 3.1.3.16 (Calcineurin)
WM0HAQ4WNM (Tacrolimus)
XVA4O219QW (Wortmannin)

Date Created: 19981015 Date Completed: 19981028 Latest Revision: 20181201

20221213

10.1038/sj.onc.1202049

9771966