Overexpression of activation transcriptional factor 1 in lymphomas and in activated lymphocytes.
cAMP-regulated gene expression always involves a conserved cAMP-responsive element (CRE) present in the promoter of cAMP-inducible genes. Two of the highly related proteins, cyclic AMP-responsive element binding protein (CREB) and activation transcriptional factor 1 (ATF-1), have been shown to activate transcription in response to cAMP by interacting with CRE. However, ATF-1 is a much weaker mediator of cAMP response, and its functional role in vivo remains unclear. Here we report a significant enhancement of ATF-1 expression in most transformed lymphocytes. Little variation in CREB level was observed, however. The activation of normal T lymphocytes induced a transient increase of ATF-1 expression to a level comparable to that of T lymphomas. Activation had no effect on the ATF-1 level of transformed T lymphocytes. The induction of ATF-1 required the costimulation of normal T lymphocytes with TPA and A23187. TPA, Ca2+ ionophore, or cAMP alone did not stimulate ATF-1 expression in normal lymphocytes. Nuclear run-on assay indicates that the increased ATF-1 expression in T cell lymphomas and in activated splenic T lymphocytes was not due to an enhanced transcription. Instead, an increase in ATF-1 mRNA stability was found in these lymphocytes. The regulation of ATF-1 expression through RNA stability in cells of different states suggests that ATF-1 may play an active role in cell growth and differentiation.
Hsueh
Y P
YP
Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
Lai
M Z
MZ
D051697:Activating Transcription Factor 1; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D004268:DNA-Binding Proteins; D004586:Electrophoresis / Q000379:methods; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006825:Hybridomas; D008213:Lymphocyte Activation / Q000502:physiology; D008223:Lymphoma / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis*
D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; D004268:DNA-Binding Proteins; D014157:Transcription Factors