Evidence map›Paper›PMID 38453366›Full record

ArticleLife science alliance2024

Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life.

David R Amici, Sammy Alhayek, Austin T Klein, Yi-Zhi Wang, Anika P Wilen, Weimin Song, Pei Zhu, Abhishek Thakkar, McKenzi A King, Adam Wt Steffeck and 4 more

Abstract read
In one paragraph

Article in Life science alliance, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
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

14 authors.

David R AmiciDepartment of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Sammy AlhayekDepartment of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0002-2351-4894
Austin T KleinDepartment of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0002-6449-9424
Yi-Zhi WangDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0001-5279-5034
Anika P WilenDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID 0000-0002-8310-9946
Weimin SongComprehensive Metabolic Core, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Pei ZhuDepartment of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Abhishek ThakkarDepartment of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
McKenzi A KingDepartment of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Adam Wt SteffeckDepartment of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Milad J AlasadyDepartment of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Clara PeekDepartment of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Jeffrey N SavasDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Marc L MendilloDepartment of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA mendillo@northwestern.edu.ORCID 0000-0001-8128-0128

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Devalingam Mahalingam · 1993 to 2026
$153.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008152 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ARDEHALI, HOSSEIN · 1987 to 2021
$24.0M
TRAINING PROGRAM IN SIGNAL TRANSDUCTION AND CANCERT32CA070085 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1997 to 2026
$5.7M
Understanding Amyloid Pathology - Multiomic Activity Imaging of Plaque Formation Dynamics (AmyMAP)R01AG078796 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Jeffrey Nicholas Savas · 2022 to 2026
$2.7M
Regulation and interplay of Heat Shock Factors in growth-associated proteotoxic stressesR01GM144617 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Marc Mendillo · 2022 to 2026
$1.6M
Orbitrap Eclipse Mass Spectrometer for Northwestern University Neuroproteomic Collaboration HubS10OD032464 · OD · NORTHWESTERN UNIVERSITY · PI SAVAS, JEFFREY NICHOLAS · 2023 to 2023
$1.3M
Elucidating the Role of C16orf72 in the Cellular Stress Response NetworkF30CA264513 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI AMICI, DAVID RUSSELL · 2021 to 2025
$222k
NCI NIH HHS F30 CA264513NCI NIH HHS P30 CA060553NCI NIH HHS T32 CA070085NIA NIH HHS R01 AG078796NIGMS NIH HHS R01 GM144617NIGMS NIH HHS T32 GM008152NIH HHS S10 OD032464
6 · The paper itself

Abstract

The recently discovered HAPSTR1 protein broadly oversees cellular stress responses. This function requires HUWE1, a ubiquitin ligase that paradoxically marks HAPSTR1 for degradation, but much about this pathway remains unclear. Here, leveraging multiplexed proteomics, we find that HAPSTR1 enables nuclear localization of HUWE1 with implications for nuclear protein quality control. We show that HAPSTR1 is tightly regulated and identify ubiquitin ligase TRIP12 and deubiquitinase USP7 as upstream regulators titrating HAPSTR1 stability. Finally, we generate conditional Hapstr1 knockout mice, finding that Hapstr1-null mice are perinatal lethal, adult mice depleted of Hapstr1 have reduced fitness, and primary cells explanted from Hapstr1-null animals falter in culture coincident with HUWE1 mislocalization and broadly remodeled signaling. Notably, although HAPSTR1 potently suppresses p53, we find that Hapstr1 is essential for life even in mice lacking p53. Altogether, we identify novel components and functional insights into the conserved HAPSTR1-HUWE1 pathway and demonstrate its requirement for mammalian life.

Indexed as

Tumor Suppressor Protein p53Ubiquitin-Protein LigasesAnimalsIntracellular Signaling Peptides and ProteinsMammalsMiceNuclear ProteinsSignal TransductionTumor Suppressor ProteinsUbiquitinUbiquitinationHAPSTR1 protein, humanHuwe1 protein, mouseIntracellular Signaling Peptides and ProteinsNuclear ProteinsTumor Suppressor Protein p53Tumor Suppressor ProteinsUbiquitinUbiquitin-Protein Ligases

Identifiers

PMID38453366
PMCPMC10921065

What OpenQuestion holds

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LicenceCC BY
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.