Gz. Yan et al., A CONSTITUTIVELY ACTIVE FORM OF CREB CAN ACTIVATE EXPRESSION OF THE RAT PROLACTIN PROMOTER IN NONPITUITARY CELLS, Molecular and cellular endocrinology, 101(1-2), 1994, pp. 180000025-180000030
The pituitary cell-specific transcription factor Pit-1 has been show t
o trans-activate expression of the prolactin (PRL) promoter in non-pit
uitary cells. However, the cyclic AMP response element (CRE)-binding p
rotein CREB is known to play a major role in cell-specific expression
of hepatocyte-specific genes. Since the PRL promoter contains an asymm
etrical form of a cyclic AMP response element (termed the CLE), we inv
estigated whether CREB could also induce PRL promoter activity in non-
pituitary cells. Transient expression in rat glial C6 cells of a const
itutively active CREB-VP16 fusion protein strongly trans-activated exp
ression of a co-transfected rat PRL promoter construct, (-187)PRL-CAT.
Analysis by 5'-deletion showed that this response requires PRL promot
er sequences between positions -113/-75. CREB-VP16 did not stimulate e
xpression in C6 cells of any of three control promoter-CAT constructs,
implying that the strong response of the PRL promoter to activated CR
EB is both promoter-specific, and is not due to non-specific transcrip
tional effects of the potent VP16 moiety of CREB-VP16. Surprisingly, m
utations in the CLE only slightly reduced activation by CREB-VP16 of c
onstruct (-204)PRL-CAT, implying that the major action of CREB-VP16 on
the PRL promoter; does not involve a direct interaction with the CLE.
CREB-VP16 stimulated PRL-CAT activity in C6 cells as strongly as, and
synergistically with, Pit-1. These results imply that CREB can strong
ly and specifically activate expression of the PRL promoter in non-pit
uitary cells, via a mechanism different from that employed by Pit-1.