Regulation of the low density lipoprotein receptor and hydroxymethylglutaryl coenzyme A reductase genes by protein kinase C and a putative negative regulatory protein.

作者: J. H. Auwerx , A. Chait , S. S. Deeb

DOI: 10.1073/PNAS.86.4.1133

关键词:

摘要: Transcription of the low density lipoprotein receptor (LDL-R) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase genes was rapidly transiently induced (8.5- 2.3-fold, respectively) early during phorbol 12-myristate 13-acetate (PMA)-induced macrophage differentiation human monocytic leukemia cell line THP-1. The levels mRNA coding for LDL-R HMG-CoA increased soon after induction, reached a maximum (12- 7-fold increase, in 2-3 hr, then returned to constitutive observed before induction. stability did not change significantly differentiation, whereas that decreased by about 5-fold 6 hr addition PMA. Transcriptional induction both (5.6- 2-fold, also when undifferentiated cells were treated with cycloheximide (CHX), resulting transient increase steady-state (7- 3-fold, respectively). These results suggest expression two is maintained at uninduced THP-1 protein short half-life. Superinduction occurred PMA CHX added simultaneously. mRNAs mediated kinase C. It hypothesized C acts directly or indirectly inactivate labile negative regulatory protein. Induction hepatocarcinoma Hep G2 CHX, suggesting this mechanism regulation may exist several types.

参考文章(32)
K L Luskey, J R Faust, D J Chin, M S Brown, J L Goldstein, Amplification of the gene for 3-hydroxy-3-methylglutaryl coenzyme A reductase, but not for the 53-kDa protein, in UT-1 cells. Journal of Biological Chemistry. ,vol. 258, pp. 8462- 8469 ,(1983) , 10.1016/S0021-9258(20)82087-0
P A Dawson, S L Hofmann, D R van der Westhuyzen, T C Südhof, M S Brown, J L Goldstein, Sterol-dependent repression of low density lipoprotein receptor promoter mediated by 16-base pair sequence adjacent to binding site for transcription factor Sp1. Journal of Biological Chemistry. ,vol. 263, pp. 3372- 3379 ,(1988) , 10.1016/S0021-9258(18)69081-7
Keiya Tada, Tasuke Konno, Shigeru Tsuchiya, Shingi Nakae, Yasuko Kobayashi, Yoichi Goto, Hidesada Okumura, Induction of Maturation in Cultured Human Monocytic Leukemia Cells by a Phorbol Diester Cancer Research. ,vol. 42, pp. 1530- 1536 ,(1982)
S Yamamoto, H Gotoh, E Aizu, R Kato, Failure of 1-oleoyl-2-acetylglycerol to mimic the cell-differentiating action of 12-O-tetradecanoylphorbol 13-acetate in HL-60 cells. Journal of Biological Chemistry. ,vol. 260, pp. 14230- 14234 ,(1985) , 10.1016/S0021-9258(17)38707-0
R J Imbra, M Karin, Metallothionein gene expression is regulated by serum factors and activators of protein kinase C Molecular and Cellular Biology. ,vol. 7, pp. 1358- 1363 ,(1987) , 10.1128/MCB.7.4.1358
P Angel, I Baumann, B Stein, H Delius, H J Rahmsdorf, P Herrlich, 12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5'-flanking region. Molecular and Cellular Biology. ,vol. 7, pp. 2256- 2266 ,(1987) , 10.1128/MCB.7.6.2256
M E Greenberg, A L Hermanowski, E B Ziff, Effect of protein synthesis inhibitors on growth factor activation of c-fos, c-myc, and actin gene transcription. Molecular and Cellular Biology. ,vol. 6, pp. 1050- 1057 ,(1986) , 10.1128/MCB.6.4.1050
Y Nishizuka, Studies and perspectives of protein kinase C Science. ,vol. 233, pp. 305- 312 ,(1986) , 10.1126/SCIENCE.3014651