Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 36, Pages 14729-14734Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1216844110
Keywords
cell differentiation; apoptosis
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Funding
- Fundacio Gent per Gent (Spain)
- Ministerio de Educacion y Ciencia (Spain) [SAF2009-10226]
- Ministerio de Educacion y Ciencia (Fondo Europeo de Desarrollo Regional) [SAF2009-10226]
- Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III-Ministerio de Sanidad (Spain)
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Mutations in PTEN-induced putative kinase 1 (PINK1) gene are associated to early-onset recessive forms of Parkinson disease. PINK1 function is related to mitochondria homeostasis, but the molecular pathways in which PINK1 is involved are largely unknown. Here, we report the identification of the embryonic ectoderm development polycomb histone-methylation modulator (EED/WAIT1) as a PINK1-interacting and -regulated protein. The PINK1: EED/WAIT1 physical interaction was mediated by the PINK1 kinase domain and the EED/WAIT1 40 amino acid ending with tryptophan and aspartate (WD40)-repeat region, and PINK1 phosphorylated EED/WAIT1 in vitro. PINK1 associated with EED/WAIT1 in cells and relocated EED/WAIT1 to the mitochondria. This interaction reduced the trimethylation of lysine 27 from histone H3, which affected polycomb-regulated gene transcription during RA differentiation of SH-SY5Y human neuroblastoma cells. Our findings unveil a pathway by which PINK1 regulates histone methylation and gene expression through the polycomb repressor complex.
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