RECONSTITUTION OF THE FUNCTIONAL GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR PROMOTER - EVIDENCE FOR DISTINCT ACTIVATION MECHANISMS THAT MEDIATE THE RESPONSE TO PHORBOL ESTER CALCIUM AND HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX SIGNALS/
N. Koyanonakagawa et al., RECONSTITUTION OF THE FUNCTIONAL GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR PROMOTER - EVIDENCE FOR DISTINCT ACTIVATION MECHANISMS THAT MEDIATE THE RESPONSE TO PHORBOL ESTER CALCIUM AND HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX SIGNALS/, International immunology, 5(4), 1993, pp. 345-352
Functional elements in the promoter region of the mouse granulocyte-ma
crophage colony stimulating factor (GM-CSF) gene were assessed by cons
tructing chimeric promoters linked to the bacterial chloramphenicol ac
etyltransferase (CAT) gene and by employing a transient transfection a
ssay of human T cell leukemia Jurkat cells. We previously reported tha
t CLE2/GC-box (at positions -95 to -73, which is homologous to the NF-
chiB binding site) and CLE0 (at positions -54 to -40) of the mouse GM-
CSF promoter are essential for transcriptional activation in response
to phorbol-12-myristate-13-acetate (PMA)/calcium ionophore (A23187). H
ere we show that CLE2/GC-box and the NF-chiB binding motif are functio
nally interchangeable and that CLE2/GC-box and CLE0 as a unit activate
the basic GM-CSF promoter in response to PMA/calcium signals. This un
it is also capable of activating heterologous promoters in response to
PMA/calcium signals. In addition, we show that Tax, the trans-activat
or encoded by human T cell leukemia virus type I (HTLV-I), activates t
he GM-CSF promoter via CLE2/GC-box without the involvement of CLE0. Th
ese results indicate that PMA/A23187-dependent and Tax-dependent activ
ation of the GM-CSF gene proceeds through distinct mechanisms.