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Activation of the lifespan regulator p66Shc through reversible disulfide bond formation.

Title data

Gertz, Melanie ; Fischer, Frank ; Wolters, Dirk ; Steegborn, Clemens:
Activation of the lifespan regulator p66Shc through reversible disulfide bond formation.
In: Proceedings of the National Academy of Sciences of the United States of America. Vol. 105 (15 April 2008) Issue 15 . - pp. 5705-5709.
ISSN 1091-6490
DOI: https://doi.org/10.1073/pnas.0800691105

Abstract in another language

Cell fate and organismal lifespan are controlled by a complex signaling network whose dysfunction can cause a variety of aging-related diseases. An important protection against these failures is cellular apoptosis, which can be induced by p66(Shc) in response to cellular stress. The precise mechanisms of p66(Shc) action and regulation and the function of the p66(Shc)-specific N terminus remain to be identified. Here, we show that the p66(Shc) N terminus forms a redox module responsible for apoptosis initiation, and that this module can be activated through reversible tetramerization by forming two disulfide bonds. Glutathione and thioredoxins can reduce and inactivate p66(Shc), resulting in a thiol-based redox sensor system that initiates apoptosis once cellular protection systems cannot cope anymore with cellular stress.

Further data

Item Type: Article in a journal
Refereed: Yes
Additional notes: PubMed-ID: 16051147
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry > Chair Biochemistry - Univ.-Prof. Dr. Clemens Steegborn
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry
Result of work at the UBT: No
DDC Subjects: 500 Science > 540 Chemistry
Date Deposited: 16 Apr 2015 11:24
Last Modified: 16 Apr 2015 11:24
URI: https://eref.uni-bayreuth.de/id/eprint/10293