Regulation of Protein Quality Control by UBE4B and LSD1 through p53-Mediated Transcription

Goran Periz, Jiayin Lu, Tao Zhang, Mark W. Kankel, Angela M. Jablonski, Robert Kalb, Alexander McCampbell, Jiou Wang

Research output: Contribution to journalArticle

Abstract

Protein quality control is essential for clearing misfolded and aggregated proteins from the cell, and its failure is associated with many neurodegenerative disorders. Here, we identify two genes, ufd-2 and spr-5, that when inactivated, synergistically and robustly suppress neurotoxicity associated with misfolded proteins in Caenorhabditis elegans. Loss of human orthologs ubiquitination factor E4 B (UBE4B) and lysine-specific demethylase 1 (LSD1), respectively encoding a ubiquitin ligase and a lysine-specific demethylase, promotes the clearance of misfolded proteins in mammalian cells by activating both proteasomal and autophagic degradation machineries. An unbiased search in this pathway reveals a downstream effector as the transcription factor p53, a shared substrate of UBE4B and LSD1 that functions as a key regulator of protein quality control to protect against proteotoxicity. These studies identify a new protein quality control pathway via regulation of transcription factors and point to the augmentation of protein quality control as a wide-spectrum antiproteotoxicity strategy.

Original languageEnglish (US)
Article numbere1002114
JournalPLoS biology
Volume13
Issue number4
DOIs
StatePublished - Apr 2 2015

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint Dive into the research topics of 'Regulation of Protein Quality Control by UBE4B and LSD1 through p53-Mediated Transcription'. Together they form a unique fingerprint.

  • Cite this