HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sinensky, M. Articles by Pinkerton, F. Search for Related Content PubMed PubMed Citation Articles by Sinensky, M. Articles by Pinkerton, F. Social Bookmarking                      What's this?

JBC, Vol. 254, Issue 11, 4482-4486, Jun, 1979

Defective regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in a somatic cell mutant

M. Sinensky, G. Duwe and F. Pinkerton

A somatic cell mutant of the CHO-K1 cell selected to be resistant to the killing effects of 25-hydroxycholesterol in the absence of cholesterol is shown to be defective in the inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity by 25-hydroxycholesterol, cholesterol, and lipoproteins, thus maintaining the enzyme activity found in cells in the absence of exogenous sterol constitutively. The mutants phenotype is shown to be dominant with respect to the wild type. Actinomycin D and cycloheximide prevent the increase of HMG-CoA reductase activity that occurs in the CHO-K1 cell when cholesterol is removed from medium. Degradation of the enzyme, measured during inhibition of protein synthesis by cycloheximide, occurs at the same rate in the mutant as in the wild type. Kinetic studies indicate that the Km for two substrates, the activation energy, and a break in the Arrhenius plot are the same for HMG-CoA reductase determined in wild type and mutant cells. From these studies it is concluded that the mutant is defective in the regulation of synthesis of HMG-CoA reductase. Of the four processes which determine cellular cholesterol levels: biosynthesis, esterification, efflux, and uptake, only biosynthesis is altered, demonstrating that these processes are not co-ordinately controlled as has been suggested previously.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Mitra, I. Ubarretxena-Belandia, T. Taguchi, G. Warren, and D. M. Engelman Modulation of the bilayer thickness of exocytic pathway membranes by membrane proteins rather than cholesterol PNAS, March 23, 2004; 101(12): 4083 - 4088. [Abstract] [Full Text] [PDF]

				A. E. Rusinol, L. Yang, D. Thewke, S. R. Panini, M. F. Kramer, and M. S. Sinensky Isolation of a Somatic Cell Mutant Resistant to the Induction of Apoptosis by Oxidized Low Density Lipoprotein J. Biol. Chem., March 15, 2000; 275(10): 7296 - 7303. [Abstract] [Full Text] [PDF]

				J Yang, R Sato, J L Goldstein, and M S Brown Sterol-resistant transcription in CHO cells caused by gene rearrangement that truncates SREBP-2. Genes & Dev., August 15, 1994; 8(16): 1910 - 1919. [Abstract] [PDF]