Human LBP-32/MGR is a repressor of the P450scc in human choriocarcinoma cell line JEG-3.
Steroid hormones regulate a wide range of physiologic functions in humans. The cholesterol side-chain cleavage enzyme P450scc regulates the initial step of biosynthesis of all steroid hormones. We investigated the expression of P450scc by studying a potential regulator of P450scc, LBP-32/MGR. Using a Northern blot, we found that LBP-32/MGR mRNA was expressed mainly in the human placenta. Using radiation hybrid mapping, we identified LBP-32/MGR on human chromosome 2p25. Recombinant LBP-32/MGR protein bound preferentially to a DNA fragment from the promoter of P450scc in vitro and exhibited clear nuclear localization in transfected cells. Luciferase reporter gene assays showed that LBP-32/MGR specifically repressed transcriptional activation of the human P450scc promoter. Because placental P450scc expression is essential for pregnancy and steroid biosynthesis, the placental expression and transcriptional repressor activity of LBP-32/MGR in JEG-3 cells suggest it has a role as a transcriptional modulator of steroid biosynthesis.
Henderson
Y C
YC
Department of Head & Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Frederick
M J
MJ
Jayakumar
A
A
Choi
Y
Y
Wang
M T
MT
Kang
Y
Y
Evans
R
R
Spring
P M
PM
Uesugi
M
M
Clayman
G L
GL
D002461:Cell Line, Transformed; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000502:physiology*; D002889:Chromosomes, Human, Pair 2; D004247:DNA / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C518352:GRHL1 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; D004247:DNA; D002786:Cholesterol Side-Chain Cleavage Enzyme