Evidence map›Paper›PMID 38014285›Full record

ArticlebioRxiv : the preprint server for biology2023

Reversible histone deacetylase activity catalyzes lysine acylation.

Takeshi Tsusaka, Mohd Altaf Najar, Benjamin Schwarz, Eric Bohrnsen, Juan A Oses-Prieto, Christina Lee, Alma L Burlingame, Catharine M Bosio, George M Burslem, Emily L Goldberg

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. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed, 6 citations in OpenAlex.

  1. Ketone bodies as chemical signals for the immune system.American journal of physiology. Cell physiology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Takeshi TsusakaDepartment of Physiology, University of California, San Francisco; San Francisco, CA, 94158, USA.ORCID 0009-0003-3749-9749
Mohd Altaf NajarDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, 19104, USA.
Benjamin SchwarzImmunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases; Hamilton, MT, 59840, USA.
Eric BohrnsenImmunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases; Hamilton, MT, 59840, USA.
Juan A Oses-PrietoDepartment of Pharmaceutical Chemistry, University of California, San Francisco; San Francisco, CA, 94158, USA.
Christina LeeDepartment of Molecular and Cell Biology, University of California, Berkeley; Berkeley, CA, 94720, USA.
Alma L BurlingameDepartment of Pharmaceutical Chemistry, University of California, San Francisco; San Francisco, CA, 94158, USA.
Catharine M BosioImmunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases; Hamilton, MT, 59840, USA.
George M BurslemDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA, 19104, USA.
Emily L GoldbergDepartment of Physiology, University of California, San Francisco; San Francisco, CA, 94158, USA.ORCID 0000-0002-3848-6590
University of California, San Francisco · USNational Institute of Allergy and Infectious Diseases · USUniversity of Pennsylvania · USUniversity of California, Berkeley · US

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Holger Willenbring · 1986 to 2026
$30.7M
Editing Acetylation and Protein HomeostasisR35GM142505 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI George Burslem · 2021 to 2026
$2.7M
Impact of ketone bodies on age-related inflammation and healthspan extensionR00AG058801 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOLDBERG, EMILY LAUREN · 2020 to 2022
$743k
NIA NIH HHS R00 AG058801NIDDK NIH HHS P30 DK026743NIGMS NIH HHS R35 GM142505
6 · The paper itself

Abstract

Starvation and low carbohydrate diets lead to the accumulation of the ketone body, β-hydroxybutyrate (BHB), whose blood concentrations increase more than 10-fold into the millimolar range. In addition to providing a carbon source, BHB accumulation triggers lysine β-hydroxybutyrylation (Kbhb) of proteins via unknown mechanisms. As with other lysine acylation events, Kbhb marks can be removed by histone deacetylases (HDACs). Here, we report that class I HDACs unexpectedly catalyze protein lysine modification with β-hydroxybutyrate (BHB). Mutational analyses of the HDAC2 active site reveal a shared reliance on key amino acids for classical deacetylation and non-canonical HDAC-catalyzed β-hydroxybutyrylation. Also consistent with reverse HDAC activity, Kbhb formation is driven by mass action and substrate availability. This reverse HDAC activity is not limited to BHB but also extends to multiple short-chain fatty acids. The reversible activity of class I HDACs described here represents a novel mechanism of PTM deposition relevant to metabolically-sensitive proteome modifications.

Identifiers

PMID38014285
PMCPMC10680841
OpenAlexW4388751312

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.