ZMPSTE24, an integral membrane zinc metalloprotease with a connection to progeroid disorders

Jemima Barrowman, Susan Michaelis

Research output: Contribution to journalReview articlepeer-review

Abstract

ZMPSTE24 is an integral membrane zinc metalloprotease originally discovered in yeast as an enzyme (called Ste24p) required for maturation of the mating pheromone a-factor. Surprisingly, ZMPSTE24 has recently emerged as a key protease involved in human progeroid disorders. ZMPSTE24 has only one identified mammalian substrate, the precursor of the nuclear scaffold protein lamin A. ZMPSTE24 performs a critical endoproteolytic cleavage step that removes the hydrophobic farnesyl-modified tail of prelamin A. Failure to do so has drastic consequences for human health and longevity. Here, we discuss the discovery of the yeast and mammalian ZMPSTE24 orthologs and review the unexpected connection between ZMPSTE24 and premature aging.

Original languageEnglish (US)
Pages (from-to)761-773
Number of pages13
JournalBiological Chemistry
Volume390
Issue number8
DOIs
StatePublished - Aug 1 2009

Keywords

  • A-factor
  • Hutchinson-Gilford Progeria Syndrome (HGPS)
  • Mandibuloacral dysplasia (MAD)
  • Prelamin A
  • Restrictive dermopathy (RD)
  • Ste24

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

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