Evidence map›Paper›PMID 37595557›Full record

ArticleMolecular cell2023

Molecular mechanism for activation of the 26S proteasome by ZFAND5.

Donghoon Lee, Yanan Zhu, Louis Colson, Xiaorong Wang, Siyi Chen, Emre Tkacik, Lan Huang, Qi Ouyang, Alfred L Goldberg, Ying Lu

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

16 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Structures of the 26Science advances · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Structural insights into the ubiquitin-independent midnolin-proteasome pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Proteasome: Role in T Cell Function Regulation.International journal of biological sciences · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Donghoon LeeDepartment of Cell Biology, Harvard Medical School, Boston, MA USA.
Yanan ZhuDepartment of Systems Biology, Harvard Medical School, Boston, MA USA; Center for Quantitative Biology, Peking University, Beijing, China; State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, China.
Louis ColsonDepartment of Systems Biology, Harvard Medical School, Boston, MA USA.
Xiaorong WangSchool of Medicine, University of California Irvine, Irvine, Irvine, CA USA.
Siyi ChenDepartment of Systems Biology, Harvard Medical School, Boston, MA USA.
Emre TkacikDepartment of Systems Biology, Harvard Medical School, Boston, MA USA.
Lan HuangSchool of Medicine, University of California Irvine, Irvine, Irvine, CA USA.
Qi OuyangCenter for Quantitative Biology, Peking University, Beijing, China; State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Alfred L GoldbergDepartment of Cell Biology, Harvard Medical School, Boston, MA USA. Electronic address: alfred_goldberg@hms.harvard.edu.
Ying LuDepartment of Systems Biology, Harvard Medical School, Boston, MA USA. Electronic address: ying_lu@hms.harvard.edu.
Harvard University · USUniversity of California, Irvine · USPeking University · CN

Funding

MOLECULAR CHAPERONES AND PROTEIN DEGRADATIONR01GM051923 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GOLDBERG, ALFRED L · 1995 to 2020
$10.1M
Proteomics of the Proteasome Interacting NetworksR01GM074830 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI HUANG, LAN · 2005 to 2022
$6.1M
Supplement: Advancing Proteomics Technologies to Decipher the Ubiquitin-Proteasome SystemR35GM145249 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Lan Huang · 2022 to 2026
$3.2M
Determine the mechanism of recognition of ubiquitin configurations by the 26S proteasomeR01GM134064 · NIGMS · HARVARD MEDICAL SCHOOL · PI LU, YING · 2019 to 2023
$1.9M
Harvard Systems Biology Graduate ProgramT32GM135014 · NIGMS · HARVARD UNIVERSITY · PI DESAI, MICHAEL M, KLEIN, ALLON MOSHE · 2020 to 2024
$1.6M
NIGMS NIH HHS R01 GM051923NIGMS NIH HHS R01 GM074830NIGMS NIH HHS R01 GM134064NIGMS NIH HHS R35 GM145249NIGMS NIH HHS T32 GM135014
6 · The paper itself

Abstract

Various hormones, kinases, and stressors (fasting, heat shock) stimulate 26S proteasome activity. To understand how its capacity to degrade ubiquitylated proteins can increase, we studied mouse ZFAND5, which promotes protein degradation during muscle atrophy. Cryo-electron microscopy showed that ZFAND5 induces large conformational changes in the 19S regulatory particle. ZFAND5's AN1 Zn-finger domain interacts with the Rpt5 ATPase and its C terminus with Rpt1 ATPase and Rpn1, a ubiquitin-binding subunit. Upon proteasome binding, ZFAND5 widens the entrance of the substrate translocation channel, yet it associates only transiently with the proteasome. Dissociation of ZFAND5 then stimulates opening of the 20S proteasome gate. Using single-molecule microscopy, we showed that ZFAND5 binds ubiquitylated substrates, prolongs their association with proteasomes, and increases the likelihood that bound substrates undergo degradation, even though ZFAND5 dissociates before substrate deubiquitylation. These changes in proteasome conformation and reaction cycle can explain the accelerated degradation and suggest how other proteasome activators may stimulate proteolysis.

Indexed as

Proteasome Endopeptidase ComplexAdenosine TriphosphatasesAnimalsCryoelectron MicroscopyCytoplasmDNA-Binding ProteinsMiceAdenosine TriphosphatasesATP dependent 26S proteaseDNA-Binding ProteinsProteasome Endopeptidase ComplexZfand5 protein, mousemuscle atrophyproteasome activationproteasomesprotein degradationubiquitinZFAND5

Identifiers

PMID37595557
PMCPMC10523585
OpenAlexW4385949374

What OpenQuestion holds

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LicenceTDM
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.