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Foti R.,International School for Advanced Studies | Zucchelli S.,International School for Advanced Studies | Zucchelli S.,Italian Institute of Technology | Zucchelli S.,Giovanni Armenise Harvard Foundation Laboratory | And 14 more authors.
Journal of Biological Chemistry | Year: 2010

Mutations in PARK7/DJ-1 are associated with autosomal recessive, early onset Parkinson disease (PD). DJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. Here we show that DJ-1 plays an essential role in the expression of rearranged during transfection (RET), a receptor for the glial cell line-derived neurotrophic factor, a neuroprotective molecule for dopaminergic neurons, the main target of degeneration in PD. The inducible loss of DJ-1 triggers the establishment of hypoxia and the production of reactive oxygen species that stabilize the hypoxia-inducible factor-1α (HIF-1a). HIF-1a expression is required for RET down-regulation. This study establishes for the first time a molecular link between the lack of functional DJ-1 and the glial cell line-derived neurotrophic factor signaling pathway that may explain the adult-onset loss of dopaminergic neurons. Furthermore, it suggests that hypoxia may play an important role in PD. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Source


Vilotti S.,International School for Advanced Studies | Vilotti S.,Giovanni Armenise Harvard Foundation Laboratory | Biagioli M.,International School for Advanced Studies | Foti R.,Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie | And 13 more authors.
Cell Death and Differentiation | Year: 2012

TRAF and TNF receptor-associated protein (TTRAP) is a multifunctional protein that can act in the nucleus as a 5′-tyrosyl DNA phosphodiesterase and in the cytoplasm as a regulator of cell signaling. In this paper we show that in response to proteasome inhibition TTRAP accumulates in nucleolar cavities in a promyelocytic leukemia protein-dependent manner. In the nucleolus, TTRAP contributes to control levels of ribosomal RNA precursor and processing intermediates, and this phenotype is independent from its 5′-tyrosyl DNA phosphodiesterase activity. Our findings suggest a previously unidentified function for TTRAP and nucleolar cavities in ribosome biogenesis under stress. © 2012 Macmillan Publishers Limited All rights reserved. Source

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