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Cell. 2013 Aug 29;154(5):971-982. doi: 10.1016/j.cell.2013.07.037.

Identification of long-lived proteins reveals exceptional stability of essential cellular structures.

Author information

1
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
2
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
3
Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA; Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
4
Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA.
5
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: jyates@scripps.edu.
6
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: hetzer@salk.edu.

Abstract

Intracellular proteins with long lifespans have recently been linked to age-dependent defects, ranging from decreased fertility to the functional decline of neurons. Why long-lived proteins exist in metabolically active cellular environments and how they are maintained over time remains poorly understood. Here, we provide a system-wide identification of proteins with exceptional lifespans in the rat brain. These proteins are inefficiently replenished despite being translated robustly throughout adulthood. Using nucleoporins as a paradigm for long-term protein persistence, we found that nuclear pore complexes (NPCs) are maintained over a cell's life through slow but finite exchange of even its most stable subcomplexes. This maintenance is limited, however, as some nucleoporin levels decrease during aging, providing a rationale for the previously observed age-dependent deterioration of NPC function. Our identification of a long-lived proteome reveals cellular components that are at increased risk for damage accumulation, linking long-term protein persistence to the cellular aging process. PAPERCLIP.

PMID:
23993091
PMCID:
PMC3788602
DOI:
10.1016/j.cell.2013.07.037
[Indexed for MEDLINE]
Free PMC Article

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