Evidence map›Paper›PMID 35110592›Full record

ArticleScientific reports2022

Structure-based prediction of HDAC6 substrates validated by enzymatic assay reveals determinants of promiscuity and detects new potential substrates.

Julia K Varga, Kelsey Diffley, Katherine R Welker Leng, Carol A Fierke, Ora Schueler-Furman

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.0field-weighted citation impact, top 28% of its field
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

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. Role of HDAC6 in carcinomas.Discover oncology · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Axonal Transport Defect in Gigaxonin Deficiency Rescued by Tubastatin A.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance.International journal of molecular sciences · 2022
    Review
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

5 authors at 2 institutions in 2 countries.

Julia K Varga *Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University of Jerusalem, Faculty of Medicine, POB 12272, 9112102, Jerusalem, Israel.
Kelsey Diffley *Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, MI, 48109, USA.
Katherine R Welker LengDepartment of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, MI, 48109, USA.
Carol A FierkeDepartment of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, MI, 48109, USA.
Ora Schueler-FurmanDepartment of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University of Jerusalem, Faculty of Medicine, POB 12272, 9112102, Jerusalem, Israel. ora.furman-schueler@mail.huji.ac.il.
University of Michigan–Ann Arbor · USHebrew University of Jerusalem · IL

Funding

STRUCTURE/FUNCTION OF ZINC METALLOPROTEINSR01GM040602 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FIERKE, CAROL A · 1993 to 2017
$6.0M
NIGMS NIH HHS R01 GM040602
6 · The paper itself

Abstract

Histone deacetylases play important biological roles well beyond the deacetylation of histone tails. In particular, HDAC6 is involved in multiple cellular processes such as apoptosis, cytoskeleton reorganization, and protein folding, affecting substrates such as ɑ-tubulin, Hsp90 and cortactin proteins. We have applied a biochemical enzymatic assay to measure the activity of HDAC6 on a set of candidate unlabeled peptides. These served for the calibration of a structure-based substrate prediction protocol, Rosetta FlexPepBind, previously used for the successful substrate prediction of HDAC8 and other enzymes. A proteome-wide screen of reported acetylation sites using our calibrated protocol together with the enzymatic assay provide new peptide substrates and avenues to novel potential functional regulatory roles of this promiscuous, multi-faceted enzyme. In particular, we propose novel regulatory roles of HDAC6 in tumorigenesis and cancer cell survival via the regulation of EGFR/Akt pathway activation. The calibration process and comparison of the results between HDAC6 and HDAC8 highlight structural differences that explain the established promiscuity of HDAC6.

Indexed as

AnimalsEnzyme AssaysHistone Deacetylase 6HumansProtein ConformationSubstrate SpecificityZebrafishZebrafish ProteinsHistone Deacetylase 6Zebrafish Proteins

Identifiers

PMID35110592
PMCPMC8810773
OpenAlexW4210327880

What OpenQuestion holds

Textmetadata
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.