Evidence map›Paper›PMID 37131806›Full record

ArticlebioRxiv : the preprint server for biology2023

Pharmacological inhibition of CLK2 activates YAP by promoting alternative splicing of AMOTL2.

Maya L Bulos, Edyta M Grzelak, Chloris Li-Ma, Emily Chen, Mitchell Hull, Kristen A Johnson, Michael J Bollong

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, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Maya L BulosDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Edyta M GrzelakDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Chloris Li-MaDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Emily ChenCalibr, A Division of Scripps Research, La Jolla, CA, 92037, USA.
Mitchell HullCalibr, A Division of Scripps Research, La Jolla, CA, 92037, USA.
Kristen A JohnsonCalibr, A Division of Scripps Research, La Jolla, CA, 92037, USA.
Michael J BollongDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Scripps Research Institute · USScripps Institution of Oceanography · US

Funding

Methods and approaches to expand the pharmacological toolsetR35GM146865 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI Michael J Bollong · 2022 to 2026
$2.3M
NIGMS NIH HHS R35 GM146865
6 · The paper itself

Abstract

Yes-associated protein (YAP), the downstream effector of the evolutionarily conserved Hippo pathway, promotes cellular proliferation and coordinates certain regenerative responses in mammals. Small molecule activators of YAP may therefore display therapeutic utility in treating disease states involving insufficient proliferative repair. From a high-throughput chemical screen of the comprehensive drug repurposing library ReFRAME, here we report the identification of SM04690, a clinical stage inhibitor of CLK2, as a potent activator of YAP driven transcriptional activity in cells. CLK2 inhibition promotes alternative splicing of the Hippo pathway protein AMOTL2, producing an exon-skipped gene product that can no longer associate with membrane-bound proteins, resulting in decreased phosphorylation and membrane localization of YAP. This study reveals a novel mechanism by which pharmacological perturbation of alternative splicing inactivates the Hippo pathway and promotes YAP dependent cellular growth.

Identifiers

PMID37131806
PMCPMC10153145
OpenAlexW4366551356

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.