Evidence map›Paper›PMID 38464278›Full record

ArticlebioRxiv : the preprint server for biology2024

Structural Requirements for Activity of Mind bomb1 in Notch Signaling.

Ruili Cao, Oren Gozlan, Lena Tveriakhina, Haixia Zhou, Hanjie Jiang, Philip A Cole, Jon C Aster, David Sprinzak, Stephen C Blacklow

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

Article in bioRxiv : the preprint server for biology, 2024. 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

9 authors at 3 institutions in 2 countries.

Ruili CaoDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Oren GozlanGeorge S. Wise Faculty of Life Sciences, School of Neurobiology, Biochemistry, and Biophysics, Tel Aviv University, Tel Aviv 69978, Israel.
Lena TveriakhinaDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Haixia ZhouDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Hanjie JiangDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Philip A ColeDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Jon C AsterDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA.
David SprinzakGeorge S. Wise Faculty of Life Sciences, School of Neurobiology, Biochemistry, and Biophysics, Tel Aviv University, Tel Aviv 69978, Israel.
Stephen C BlacklowDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-6904-1981
Harvard University · USBrigham and Women's Hospital · USTel Aviv University · IL

Funding

Chemical Approaches to Protein PhosphorylationR01CA074305 · NCI · JOHNS HOPKINS UNIVERSITY · PI COLE, PHILIP A · 2002 to 2025
$8.0M
Notch Signaling in CancerR35CA220340 · NCI · HARVARD MEDICAL SCHOOL · PI BLACKLOW, STEPHEN C. · 2017 to 2023
$7.1M
NCI NIH HHS R01 CA074305NCI NIH HHS R35 CA220340
6 · The paper itself

Abstract

Mind bomb 1 (MIB1) is a RING E3 ligase that ubiquitinates Notch ligands, a necessary step for induction of Notch signaling. The structural basis for binding of the JAG1 ligand by the N-terminal region of MIB1 is known, yet how the ankyrin (ANK) and RING domains of MIB1 cooperate to catalyze ubiquitin transfer from E2~Ub to Notch ligands remains unclear. Here, we show that the third RING domain and adjacent coiled coil region of MIB1 (ccRING3) drives MIB1 dimerization and that ubiquitin transfer activity of MIB1 relies solely on RING3. We report x-ray crystal structures of a UbcH5B-ccRING3 complex as a fusion protein and of the ANK region. Directly tethering the N-terminal region to ccRING3 forms a minimal MIB1 protein, which is sufficient to induce a Notch response in receiver cells. Together, these studies define the functional elements of an E3 ligase needed for ligands to induce a Notch signaling response.

Identifiers

PMID38464278
PMCPMC10925295
OpenAlexW4392342792

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.