Evidence map›Paper›PMID 37645969›Full record

ArticlebioRxiv : the preprint server for biology2023

Phosphorylation of a Cleaved Tau Proteoform at a Single Residue Inhibits Binding to the E3 Ubiquitin Ligase, CHIP.

Cory M Nadel, Kristin Wucherer, Abby Oehler, Aye C Thwin, Koli Basu, Matthew D Callahan, Daniel R Southworth, Daniel A Mordes, Charles S Craik, Jason E Gestwicki

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Cory M NadelDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158.
Kristin WuchererDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158.
Abby OehlerInstitute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA 94158.
Aye C ThwinDepartment of Biochemistry & Biophysics, University of California San Francisco, San Francisco, CA 94158.
Koli BasuDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158.
Matthew D CallahanDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158.
Daniel R SouthworthDepartment of Biochemistry & Biophysics, University of California San Francisco, San Francisco, CA 94158.
Daniel A MordesDepartment of Pathology, University of California San Francisco, San Francisco, CA 94158.
Charles S CraikDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158.
Jason E GestwickiDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158.
University of California, San Francisco · US

Funding

TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, YADONG · 2004 to 2018
$27.1M
Probing the Role of Chaperone-TPR Complexes in Tau ProteostasisRF1AG068125 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIK, CHARLES SCOTT, GESTWICKI, JASON E · 2020 to 2020
$2.2M
Probing the Role of Chaperone-TPR Complexes in Tau ProteostasisR01AG068125 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIK, CHARLES SCOTT, GESTWICKI, JASON E · 2024 to 2024
$569k
Decoding the molecular logic of TPR cochaperonesF31AG077842 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CALLAHAN, MATTHEW · 2022 to 2022
$39k
NIA NIH HHS F31 AG077842NIA NIH HHS P01 AG019724NIA NIH HHS P50 AG023501NIA NIH HHS R01 AG068125NIA NIH HHS RF1 AG068125
6 · The paper itself

Abstract

Microtubule-associated protein tau (MAPT/tau) accumulates in a family of neurodegenerative diseases, including Alzheimer's disease (AD). In disease, tau is aberrantly modified by post-translational modifications (PTMs), including hyper-phosphorylation. However, it is often unclear which of these PTMs contribute to tau's accumulation or what mechanisms might be involved. To explore these questions, we focused on a cleaved proteoform of tau (tauC3), which selectively accumulates in AD and was recently shown to be degraded by its direct binding to the E3 ubiquitin ligase, CHIP. Here, we find that phosphorylation of tauC3 at a single residue, pS416, is sufficient to block its interaction with CHIP. A co-crystal structure of CHIP bound to the C-terminus of tauC3 revealed the mechanism of this clash and allowed design of a mutation (CHIP

Identifiers

PMID37645969
PMCPMC10462110
OpenAlexW4385952960

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.