Evidence map›Paper›PMID 26655835›Full record

ArticleNature cell biology2016

Site-specific proteasome phosphorylation controls cell proliferation and tumorigenesis.

Xing Guo, Xiaorong Wang, Zhiping Wang, Sourav Banerjee, Jing Yang, Lan Huang, Jack E Dixon

Open access · greenAbstract read
In one paragraph

Article in Nature cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed
7.2field-weighted citation impact, top 2% 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

112 citing papers in PubMed, 169 citations in OpenAlex.

  1. Review
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  4. Article
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  7. Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025
    Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. DNA damage-induced proteasome phosphorylation controls substrate recognition and facilitates DNA repair.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  14. RNF212B E3 ligase is essential for crossover designation and maturation during male and female meiosis in the mouse.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Article
  16. Proteasome condensate formation is driven by multivalent interactions with shuttle factors and ubiquitin chains.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  17. Review
  18. Article
  19. Review
  20. Review

52 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Xing GuoDepartment of Pharmacology, University of California-San Diego, La Jolla, California 92093, USA.
Xiaorong WangDepartments of Physiology and Biophysics and of Developmental and Cell Biology, University of California, Irvine, California 92697, USA.
Zhiping WangDivision of Biological Sciences, University of California-San Diego, La Jolla, California 92093, USA.
Sourav BanerjeeDepartment of Pharmacology, University of California-San Diego, La Jolla, California 92093, USA.
Jing YangDepartment of Pharmacology, University of California-San Diego, La Jolla, California 92093, USA.
Lan HuangDepartments of Physiology and Biophysics and of Developmental and Cell Biology, University of California, Irvine, California 92697, USA.
Jack E DixonDepartment of Pharmacology, University of California-San Diego, La Jolla, California 92093, USA.
University of California, San Diego · USUniversity of California, Irvine · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
REGULATION OF NEUROPEPTIDE BIOSYNTHESISR01DK018849 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DIXON, JACK E, WORBY, CAROLYN ANN · 1986 to 2020
$7.0M
Proteomics of the Proteasome Interacting NetworksR01GM074830 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI HUANG, LAN · 2005 to 2022
$6.1M
Regulation of Tumor Invasion and Metastasis by Matrix StiffnessR01CA174869 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jing Yang · 2015 to 2026
$4.3M
STUDIES ON PANCREATIC HORMONESR01DK018024 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIXON, JACK E, WORBY, CAROLYN ANN · 1986 to 2018
$2.1M
Regulation of Tumor Invasion by Twist1R01CA168689 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YANG, JING · 2012 to 2016
$1.7M
NCI NIH HHS 1R01CA168689NCI NIH HHS 1R01CA174869NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA168689NCI NIH HHS R01 CA174869NIDDK NIH HHS R01 DK018024NIDDK NIH HHS R01 DK018849NIDDK NIH HHS R01DK018849NIGMS NIH HHS R01 GM074830NIGMS NIH HHS R01GM074830
6 · The paper itself

Abstract

Despite the fundamental importance of proteasomal degradation in cells, little is known about whether and how the 26S proteasome itself is regulated in coordination with various physiological processes. Here we show that the proteasome is dynamically phosphorylated during the cell cycle at Thr 25 of the 19S subunit Rpt3. CRISPR/Cas9-mediated genome editing, RNA interference and biochemical studies demonstrate that blocking Rpt3-Thr25 phosphorylation markedly impairs proteasome activity and impedes cell proliferation. Through a kinome-wide screen, we have identified dual-specificity tyrosine-regulated kinase 2 (DYRK2) as the primary kinase that phosphorylates Rpt3-Thr25, leading to enhanced substrate translocation and degradation. Importantly, loss of the single phosphorylation of Rpt3-Thr25 or knockout of DYRK2 significantly inhibits tumour formation by proteasome-addicted human breast cancer cells in mice. These findings define an important mechanism for proteasome regulation and demonstrate the biological significance of proteasome phosphorylation in regulating cell proliferation and tumorigenesis.

Indexed as

Cell ProliferationAnimalsATPases Associated with Diverse Cellular ActivitiesBreast NeoplasmsCell CycleCell Line, TumorCell Transformation, NeoplasticCRISPR-Cas SystemsDyrk KinasesFemaleGene Expression Regulation, NeoplasticHeterograftsHumansMice, NudePhosphorylationProteasome Endopeptidase ComplexATPases Associated with Diverse Cellular ActivitiesDyrk KinasesProteasome Endopeptidase ComplexProtein Serine-Threonine KinasesProtein-Tyrosine KinasesPSMC4 protein, humanThreonine

Identifiers

PMID26655835
PMCPMC4844191
OpenAlexW2195466096

What OpenQuestion holds

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Registered trials

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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.