Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Squalene synthase: structure and regulation.

T R Tansey1, I Shechter

  • 1Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.

Progress in Nucleic Acid Research and Molecular Biology
|September 29, 2000
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer.

Prostate cancer and prostatic diseases·2012
Same author

Post resuscitative and initial utility in life saving efforts (pulse): a workshop executive summary.

Resuscitation·2001
Same author

Comparative squalene synthase gene expression in mouse liver and testis.

Archives of biochemistry and biophysics·2001
Same author

Farnesyl diphosphate synthase is abundantly expressed and regulated by androgen in rat prostatic epithelial cells.

The Journal of steroid biochemistry and molecular biology·2001
Same author

Workshop executive summary report: postresuscitative and initial utility in life-saving efforts (PULSE), June 29-30, 2000, Lansdowne Resort and Conference Center, Leesburg, VA.

Critical care medicine·2001
Same author

Workshop Executive Summary Report: Post-resuscitative and initial Utility in Life Saving Efforts (PULSE): June 29-30, 2000; Lansdowne Resort and Conference Center; Leesburg, VA.

Circulation·2001

Squalene synthase (SQS) regulates sterol biosynthesis by controlling metabolic flux. Its activity, protein levels, and gene transcription are tightly controlled by cellular cholesterol levels.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Metabolic Pathways

Background:

  • Squalene synthase (SQS) is a key enzyme in the isoprenoid metabolic pathway, specifically catalyzing the first committed step in sterol biosynthesis.
  • Regulation of SQS activity is crucial for directing metabolic intermediates towards either sterol or non-sterol pathways based on cellular needs.
  • Understanding SQS function is vital for comprehending cholesterol metabolism and its regulation.

Purpose of the Study:

  • To investigate the mechanism, structure, and regulation of SQS.
  • To identify key residues essential for SQS enzymatic function through site-directed mutagenesis.
  • To elucidate the transcriptional control mechanisms of the human SQS (hSQS) gene, particularly its promoter region and interactions with transcription factors.

Main Methods:

Related Experiment Videos

  • Site-directed mutagenesis of rat SQS to identify functionally important amino acid residues (Tyr, Phe, Asp).
  • Analysis of SQS activity, protein levels, and gene transcription in response to varying cholesterol levels.
  • Investigation of the human SQS gene promoter, including identification of binding sites for sterol regulatory element-binding proteins (SREBPs) and accessory transcription factors.

Main Results:

  • Conserved Tyr, Phe, and Asp residues were identified as essential for SQS function, with Tyr and Phe potentially stabilizing carbocation intermediates and Asp involved in substrate binding.
  • SQS activity, protein abundance, and gene transcription are coordinately regulated by cellular cholesterol status, decreasing with excess cholesterol and increasing with deficiency.
  • The human SQS gene promoter exhibits complex regulation with multiple binding sites for SREBP-1a and SREBP-2, which differentially contribute to promoter activation.

Conclusions:

  • SQS plays a critical role in sterol biosynthesis, with its function and regulation being finely tuned by cellular cholesterol homeostasis.
  • Specific amino acid residues are critical for SQS catalytic activity, highlighting the enzyme's structural and functional importance.
  • Transcriptional regulation of the hSQS gene involves intricate interactions between SREBPs and accessory factors, providing a sophisticated mechanism for controlling cholesterol synthesis.