Evidence map›Paper›PMID 25228775›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Identification of long-lived proteins retained in cells undergoing repeated asymmetric divisions.

Nathaniel H Thayer, Christina K Leverich, Matthew P Fitzgibbon, Zara W Nelson, Kiersten A Henderson, Philip R Gafken, Jessica J Hsu, Daniel E Gottschling

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 93 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Cell membrane asymmetries and cellular aging.The Biochemical journal · 2025
    Review
  5. Article
  6. Article
  7. Unusually Rapid Isomerization of Aspartic Acid in Tau.bioRxiv : the preprint server for biology · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Plasma Membrane MCC/Eisosome Domains Promote Stress Resistance in Fungi.Microbiology and molecular biology reviews : MMBR · 2020
    Review
  17. Article
  18. Article
  19. Article
  20. Principles and mechanisms of asymmetric cell division.Development (Cambridge, England) · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Nathaniel H ThayerDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and The Molecular and Cellular Biology Program, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA 98109.
Christina K LeverichDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and.
Matthew P FitzgibbonDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and.
Zara W NelsonDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and.
Kiersten A HendersonDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and.
Philip R GafkenDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and.
Jessica J HsuDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and The Molecular and Cellular Biology Program, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA 98109.
Daniel E GottschlingDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; and dgottsch@fhcrc.org.
Fred Hutch Cancer Center · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAUniversity of Washington · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
TRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0M
Chromosome Metabolism and Cancer Training GrantT32CA009657 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI EISENMAN, ROBERT NEIL · 1991 to 2020
$7.6M
Mechanism of increase genomic instability in aging yeastR01AG023779 · NIA · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PARKHURST, SUSAN M · 2004 to 2019
$4.2M
Dissecting the mechanism of increased genomic instability in aging yeastR37AG023779 · NIA · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GOTTSCHLING, DANIEL E. · 2010 to 2015
$2.9M
Mechanisms of organelle deteriorationR01AG037512 · NIA · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GOTTSCHLING, DANIEL E. · 2011 to 2015
$2.2M
A Genome-wide Approach to Identify the Limitations of Life SpanF31AG041579 · NIA · FRED HUTCHINSON CANCER RESEARCH CENTER · PI THAYER, NATHANIEL · 2011 to 2015
$142k
Age-Induced Defects in DNA RepairF30AG032808 · NIA · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HSU, JESSICA · 2008 to 2010
$104k
NCI NIH HHS P30 CA015704NCI NIH HHS T32 CA009657NCI NIH HHS T32CA009657NIA NIH HHS AG023779NIA NIH HHS AG037512NIA NIH HHS F30 AG032808NIA NIH HHS F30AG032808NIA NIH HHS F31 AG041579NIA NIH HHS F31AG041579NIA NIH HHS R01 AG023779NIA NIH HHS R01 AG037512NIA NIH HHS R37 AG023779NIGMS NIH HHS T32 GM007270NIGMS NIH HHS T32GM07270
6 · The paper itself

Abstract

Long-lived proteins have been implicated in age-associated decline in metazoa, but they have only been identified in extracellular matrices or postmitotic cells. However, the aging process also occurs in dividing cells undergoing repeated asymmetric divisions. It was not clear whether long-lived proteins exist in asymmetrically dividing cells or whether they are involved in aging. Here we identify long-lived proteins in dividing cells during aging using the budding yeast, Saccharomyces cerevisiae. Yeast mother cells undergo a limited number of asymmetric divisions that define replicative lifespan. We used stable-isotope pulse-chase and total proteome mass-spectrometry to identify proteins that were both long-lived and retained in aging mother cells after ∼ 18 cells divisions. We identified ∼ 135 proteins that we designate as long-lived asymmetrically retained proteins (LARPS). Surprisingly, the majority of LARPs appeared to be stable fragments of their original full-length protein. However, 15% of LARPs were full-length proteins and we confirmed several candidates to be long-lived and retained in mother cells by time-lapse microscopy. Some LARPs localized to the plasma membrane and remained robustly in the mother cell upon cell division. Other full-length LARPs were assembled into large cytoplasmic structures that had a strong bias to remain in mother cells. We identified age-associated changes to LARPs that include an increase in their levels during aging because of their continued synthesis, which is not balanced by turnover. Additionally, several LARPs were posttranslationally modified during aging. We suggest that LARPs contribute to age-associated phenotypes and likely exist in other organisms.

Indexed as

Cell DivisionMembrane ProteinsPeptide FragmentsProteomicsRecombinant Fusion ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsMembrane ProteinsPeptide FragmentsRecombinant Fusion ProteinsSaccharomyces cerevisiae ProteinsACDasymmetric cell divisionrecombination-induced tag exchangereplicative agingRITE

Identifiers

PMID25228775
PMCPMC4191815
OpenAlexW1981840094

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.