MAP1S enhances autophagy to suppress tumorigenesis

Leyuan Liu, Wallace L. McKeehan, Fen Wang, Rui Xie

Research output: Contribution to journalShort survey

30 Scopus citations

Abstract

Microtubule-associated protein 1 small form (MAP1S; originally named C19ORF5) was identified as serving as linkers to connect mitochondria with microtubules for trafficking, and to bridge the autophagy machinery with microtubules and mitochondria to affect autophagosomal biogenesis and degradation. We found that MAP1S levels become elevated immediately in response to diethylnitrosamine-induced or genome instability-driven metabolic stress in a murine model of hepatocarcinoma. Elevation of MAP1S enhances autophagy to remove p62-associated aggresomes and dysfunctional organelles that trigger DNA double-strand (DSB) breaks and genome instability. The early accumulation of an unstable genome prior to signs of tumorigenesis suggested that genome instability causes tumorigenesis. After tumorigenesis, tumor development then triggers the activation of autophagy to reduce genome instability in tumor foci. We concluded that an increase in MAP1S levels triggers autophagy in order to suppress genome instability so that both the incidence of diethylnitrosamine- induced hepatocarcinogenesis and malignant progression are suppressed. Thus, a link between MAP1S-enhanced autophagy and suppression of genomic instability and tumorigenesis has been established.

Original languageEnglish (US)
JournalAutophagy
Volume8
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Autophagy
  • C19ORF5
  • Genome instability
  • Hepatocarcinomas
  • LRPPRC
  • MAP1S
  • Microtubules
  • Mitochondria
  • RASSF1A
  • p62

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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