Skin-specific regulation of SREBP processing and lipid biosynthesis by glycerol kinase 5

Proc Natl Acad Sci U S A. 2017 Jun 27;114(26):E5197-E5206. doi: 10.1073/pnas.1705312114. Epub 2017 Jun 12.


The recessive N-ethyl-N-nitrosourea-induced phenotype toku is characterized by delayed hair growth, progressive hair loss, and excessive accumulation of dermal cholesterol, triglycerides, and ceramides. The toku phenotype was attributed to a null allele of Gk5, encoding glycerol kinase 5 (GK5), a skin-specific kinase expressed predominantly in sebaceous glands. GK5 formed a complex with the sterol regulatory element-binding proteins (SREBPs) through their C-terminal regulatory domains, inhibiting SREBP processing and activation. In Gk5toku/toku mice, transcriptionally active SREBPs accumulated in the skin, but not in the liver; they were localized to the nucleus and led to elevated lipid synthesis and subsequent hair growth defects. Similar defective hair growth was observed in kinase-inactive GK5 mutant mice. Hair growth defects of homozygous toku mice were partially rescued by treatment with the HMG-CoA reductase inhibitor simvastatin. GK5 exists as part of a skin-specific regulatory mechanism for cholesterol biosynthesis, independent of cholesterol regulation elsewhere in the body.

Keywords: SREBP; alopecia; cholesterol biosynthesis; glycerol kinase; sebocyte.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Glycerol Kinase / genetics
  • Glycerol Kinase / metabolism*
  • Lipids / biosynthesis*
  • Lipids / genetics
  • Mice
  • Mice, Knockout
  • Protein Domains
  • Protein Processing, Post-Translational*
  • Simvastatin / pharmacology
  • Skin / metabolism*
  • Sterol Regulatory Element Binding Proteins / genetics
  • Sterol Regulatory Element Binding Proteins / metabolism*


  • Lipids
  • Sterol Regulatory Element Binding Proteins
  • Simvastatin
  • Glycerol Kinase