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Cited by 149Histone Deacetylase Inhibitors ResearchGenomics and Chromatin DynamicsEpigenetics and DNA Methylation

Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase

Open access
Moreno-Yruela, Carlos, Galleano, Iacopo, Madsen, Andreas S., Olsen, Christian A.·2018·Cell Chemical Biology
DOI 10.1016/j.chembiol.2018.04.007

Published version of a preprint

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Abstract

Histone deacetylase (HDAC) enzymes regulate diverse biological function, including gene expression, rendering them potential targets for intervention in a number of diseases, with a handful of compounds approved for treatment of certain hematologic cancers. Among the human zinc-dependent HDACs, the most recently discovered member, HDAC11, is the only member assigned to subclass IV. It is the smallest protein and has the least well understood biological function. Here, we show that HDAC11 cleaves long-chain acyl modifications on lysine side chains with remarkable efficiency. We further show that several common types of HDAC inhibitors, including the approved drugs romidepsin and vorinostat, do not inhibit this enzymatic activity. Macrocyclic hydroxamic acid-containing peptides, on the other hand, potently inhibit HDAC11 demyristoylation activity. These findings should be taken carefully into consideration in future investigations of the biological function of HDAC11 and will serve as a foundation for the development of selective chemical probes targeting HDAC11.

AI snapshot

Written from the paper’s full text.

TL;DR

HDAC11 is shown to be an efficient ε-N-myristoyllysine hydrolase, cleaving long-chain acyl groups on lysine far better than acetyl groups. Common HDAC inhibitors such as vorinostat and romidepsin do not inhibit this demyristoylation activity, whereas macrocyclic hydroxamic acid-containing peptides do.

Key findings

  • Screening all eleven human zinc-dependent HDACs against a >30-member fluorogenic ε-N-acyllysine substrate library showed HDAC11 cleaved Kmyr with high efficiency equal to class I HDAC-mediated Kac conversion, while its deacetylation activity was negligible under the chosen conditions.
  • HDAC11 demyristoylation kinetics gave kcat/KM = 1.5 × 10^4 M−1 s−1 and KM = 60 µM, with the high efficiency arising from a high kcat rather than a particularly low KM.
  • LC-MS validation with non-fluorogenic dodecapeptides showed ~25% conversion of myristoylated substrate 7 after 60 min with 20 nM HDAC11, while no product was detected from the Kac-containing substrate 8.
  • SAHA (vorinostat) and romidepsin did not significantly inhibit HDAC11 up to 100 µM; trapoxin A and hydroxamic acid-containing macrocycles such as ApiA Asuha and TpxB Asuha potently inhibited the demyristoylation activity, with ApiA Asuha showing slow, tight-binding kinetics.

Methods

  • Recombinant human HDAC1–11 were screened against an in-house library of more than thirty fluorogenic ε-N-acyllysine substrates using end-point, trypsin-coupled fluorescence assays; HDAC11 construct and buffer conditions were compared, including untagged versus GST-tagged enzyme and Tris versus HEPES pH 7.4 buffers.
  • Continuous fluorescence assays measured initial rates and inhibitor dose–response; Michaelis–Menten experiments used Ac-ETDKmyr (6e) without BSA, and LC-MS assays used dodecapeptide substrates 7 (Kac) and 8 (Kmyr).
  • Substrate scope was tested with additional long-chain, oxidized, and unsaturated acyl modifications; data were analyzed in GraphPad Prism 7.0.

Limitations

  • The paper states that it cannot rule out HDAC11 also targeting specific Kac-containing substrates in vivo and cannot exclude Kac hydrolysis under certain conditions, such as in a chromatin complex.
  • The paper states that non-charged Kmyr substrates were not soluble in aqueous media, so peptide-sequence effects could not be fully assessed and require future investigation.
  • Evident from the text: the study is primarily in vitro with recombinant enzyme and synthetic substrates; cellular or in vivo validation is not presented, and the significance section refers to cellular relevance only as personal communication.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

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Crossref · 10.1016/j.chembiol.2018.04.007

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 28 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Effects of buffer conditions, HDAC11 construct, and substrate structure

    The HEPES buffer (pH 7.4) containing 0.05 mg/mL BSA gives the highest initial rates for HDAC11 demyristoylation.

    “The HEPES buffer (pH 7.4) containing 0.05 mg/mL of BSA gave rise to the highest initial rates and, because this also has a more relevant pH, we chose this buffer for evaluation of inhibitors and additional substrates.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Substrate screening

    HDAC11 cleaves Kmyr with high efficiency equal to the conversions of Kac recorded for class I HDACs.

    “Interestingly, however, HDAC11 cleaved Kmyr with high efficiency equal to the conversions of Kac recorded for class I HDACs (orange color in the heat map, Fig. 1B).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Substrate screening

    HDAC10 did not show significant conversion of any of the substrates tested.

    “The second class IIb enzyme, HDAC10, did not show significant conversion of any of our substrates, which is in agreement with a recent report demonstrating the ability of HDAC10 to deacylate polyamines rather than lysine residues (Hai et al., 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hai et al., 2017 source

      Not checked in the free run.

  • Findingown data
    § Effects of buffer conditions, HDAC11 construct, and substrate structure

    HDAC11 deacetylation activity is negligible under the assay conditions used.

    “As also indicated in the initial screen, the deacetylation activity of the more active untagged HDAC11 was negligible under these conditions as well (Fig. 2A).”
    Quote in the paperSubstantial claim
  • Findingown data
    § HDAC11 cleaves a narrow selection of long chain acyl groups

    The negatively charged ETDK-based peptide (scaffold 6) is turned over to a significantly higher degree than the two positively charged substrates (scaffolds 4 and 5).

    “Interestingly, we observed a distinct effect on conversion depending on the peptide sequence, where the negatively charged ETDK-based peptide (scaffold 6 ) was turned over to a significantly higher degree than the two positively charged substrates (scaffolds 4 and 5 ).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 15
  • Classified as probably not a substantial claim. 20

  • May combine two claims.

    Findingown data
    § HDAC11 cleaves a narrow selection of long chain acyl groups

    Oxidation at the 3-position to hydroxyl or ketone modifications abolishes HDAC11 activity, whereas the structurally similar α,β-unsaturated substrate is cleaved.

    “Furthermore, oxidation at the 3-position to give hydroxyl ( 6æ ) or ketone ( 6ø ) modifications abolished activity while the structurally more similar a , b -unsaturated substrate ( 6z ) was cleaved (Fig. 4).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § SUMMARY

    Trapoxin A and hydroxamic acid-containing macrocyclic peptides potently inhibit HDAC11 demyristoylation activity.

    “Macrocyclic hydroxamic acid-containing peptides, on the other hand, potently inhibit HDAC11 demyristoylation activity.”
    • Also stated in: § The HDAC11 demyristoylation activity is inhibited by hydroxamic acid-containing macrocycles but not SAHA (vorinostat) · plain
      “Interestingly, the only compounds that potently inhibited HDAC11 were trapoxin A ( TpxA ) and hydroxamic acid-containing macrocyclic peptides (such as ApiA Asuha ) inspired by archetypal natural product HDAC inhibitors”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § HDAC11 cleaves a narrow selection of long chain acyl groups

    Truncation or elongation of the fatty acid chain diminishes HDAC11 activity.

    “while both truncation ( 4u , 5c , 5d , 5u , 5v , and 6d ) and elongation ( 5y ) give rise to diminished activity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Kinetic investigation of HDAC11 demyristoylation

    HDAC11 demyristoylation has a catalytic efficiency kcat/KM of 1.5 × 10^4 M^-1 s^-1 and a KM of 60 μM, with the high efficiency resulting from a high kcat rather than a particularly low KM.

    “the remarkably high enzymatic efficiency for a KDAC measured here ( k cat / K M = 1.5 ´ 10 4 M 1 s -1 ) was a result of a high k cat rather than a particularly low K M (60 µ M) (Fig. 2C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Effects of buffer conditions, HDAC11 construct, and substrate structure

    In an LC-MS assay with non-fluorogenic peptides, incubation for 60 minutes with 20 nM HDAC11 converted approximately 25% of the myristoylated substrate 7, while no trace of product 9 was observed from the Kac-containing substrate 8.

    “After incubation for 60 minutes with 20 nM of HDAC11, we observed robust conversion of approximately 25% of the myristoylated substrate 7 , while mass spectrometry analysis of the reaction with Kaccontaining substrate 8 did not show any trace of product 9 (Fig. 2B).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § DISCUSSION

    HDAC1-3 were able to cleave Kcr as well as other short chain modifications with structural similarity.

    “HDAC1-3 were able to cleave Kcr as well as other short chain modifications with structural similarity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data
    § Protein concentration assay

    The HDAC11 untagged stock solution protein concentration was 0.79 mg/mL and the GST-tagged HDAC11 stock solution concentration was 2.43 mg/mL.

    “HDAC11 untagged: 0.79 mg/mL, HDAC11 GST-tag: 2.43 mg/mL.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation
    § DISCUSSION

    Class IIa enzymes, HDAC3, HDAC8, and HDAC11 removed the non-physiological Ktfa substrate.

    “Class IIa enzymes (Lahm et al., 2007) as well as HDAC3 (Madsen and Olsen, 2012a), HDAC8 (Bradner et al., 2010), and HDAC11 (Inks et al., 2012) removed the physiologically non-relevant trifluoroacetamide (Ktfa).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Lahm et al., 2007 source

      Not checked in the free run.

    • cites Madsen and Olsen, 2012a

      Not checked in the free run.

    • cites Bradner et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data
    § HDAC11 cleaves a narrow selection of long chain acyl groups

    HDAC11 has a narrow substrate specificity, in contrast to SIRT2, which cleaves these modifications with similar activity as Kmyr.

    “This indicates a quite narrow substrate specificity in contrast to another long chain deacylase, SIRT2, which cleaves these modifications with similar activity as Kmyr (Galleano et al., 2016).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Galleano et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data
    § Effects of buffer conditions, HDAC11 construct, and substrate structure

    HDAC11 is a lysine long chain deacylase enzyme rather than a deacetylase.

    “Though we cannot rule out that HDAC11 also targets specific Kac-containing substrates in vivo this strongly suggests that HDAC11 is a lysine long chain deacylase enzyme rather than a deacetylase.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § INTRODUCTION

    The eleven zinc-dependent HDACs are categorized in class I (HDACs 1-3 and 8), class IIa (HDACs 4, 5, 7, and 9), class IIb (HDACs 6 and 10), and class IV (HDAC11).

    “the eleven zinc-dependent HDACs, which are categorized in class I (HDACs 1-3 and 8), class IIa (HDACs 4, 5, 7, and 9), class IIb (HDACs 6 and 10), and class IV (HDAC11) (Fig. 1A) (Marmorstein, 2001; Gregoretti et al., 2004).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Marmorstein, 2001 source

      Not checked in the free run.

    • cites Gregoretti et al., 2004 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § SIGNIFICANCE

    The present work developed enzyme-economical and reliable assay protocols that allow for the characterization of potential inhibitors of HDAC11.

    “In addition, we developed enzyme-economical and reliable assay protocols that allow for the characterization of potential inhibitors of HDAC11.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § INTRODUCTION

    SIRT4 cleaves Klip and Kmgc; SIRT5 regulates Kmal, Ksuc, and Kglu; SIRT2 and SIRT6 efficiently cleave Kmyr.

    “For example, SIRT4 has been shown to cleave e -N -lipoyllysine (Klip) (Mathias et al., 2014) and e -N -(3-methylglutaconyl)lysine (Kmgc) (Anderson et al., 2017), SIRT5 regulates e -N -malonyllysine (Kmal) (Du et al., 2011; Peng et al., 2011; Hirschey and Zhao, 2015; Nishida et al., 2015), e -N -succinyllysine (Ksuc) (Du et al., 2011; Park et al., 2013; Rardin et al., 2013; Hirschey and Zhao, 2015)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Mathias et al., 2014 source

      Not checked in the free run.

    • cites Anderson et al., 2017 source

      Not checked in the free run.

    • cites Du et al., 2011

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § DISCUSSION

    HDAC11 associates with HDAC6.

    “It has been shown to associate with HDAC6 (Gao et al., 2002; Cheng et al., 2014)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Gao et al., 2002 source

      Not checked in the free run.

    • cites Cheng et al., 2014 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § INTRODUCTION

    For zinc-dependent HDACs, only few examples of deacylation activities other than deacetylation have been reported and these have been weaker than their potencies against Kac.

    “For the zinc-dependent HDACs, on the other hand, only few examples of deacylation activities other than deacetylation have been reported and these have been weaker than their potencies against Kac (Madsen and Olsen, 2012a; Aramsangtienchai et al., 2016; Wei et al., 2017).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Madsen and Olsen, 2012a

      Not checked in the free run.

    • cites Aramsangtienchai et al., 2016 source

      Not checked in the free run.

    • cites Wei et al., 2017 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § Effects of buffer conditions, HDAC11 construct, and substrate structure

    Fluorophore-coupled substrates have been questioned in several contexts.

    “Finally, because fluorophore-coupled substrates have been questioned in several contexts (Kaeberlein et al., 2005; Toro et al., 2017), we validated the preference for demyristoylation over deacetylation using non-fluorogenic peptides ( 7 -9 ) in an LC-MS-based assay (Fig. 2B).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Kaeberlein et al., 2005 source

      Not checked in the free run.

    • cites Toro et al., 2017 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § INTRODUCTION

    Class I and IV enzymes are primarily located in the nucleus, class IIa enzymes shuttle between nucleus and cytosol, and class IIb enzymes are mainly localized to the cytosol.

    “Among the eleven zinc-dependent enzymes, class I and IV enzymes are primarily located in the nucleus, class IIa enzymes are shuttling between nucleus and cytosol, and class IIb enzymes are mainly localized to the cytosol (de Ruijter et al., 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites de Ruijter et al., 2003 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § INTRODUCTION

    HDAC6 has been associated with deacetylation of several cytosolic substrates including α-tubulin and p53.

    “the class IIb isozyme, HDAC6, has been associated with deacetylation of several cytosolic substrates including a -tubulin and p53 (Hubbert et al., 2002; Zhang et al., 2003; Ryu et al., 2017).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Hubbert et al., 2002 source

      Not checked in the free run.

    • cites Zhang et al., 2003 source

      Not checked in the free run.

    • cites Ryu et al., 2017 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Buffers used for in vitro enzymatic characterization

    Control wells without enzyme were included in each assay plate.

    “Control wells without enzyme were included in each plate.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § DISCUSSION

    HDAC11 is implicated in immune response cascades and regulates expression of the anti-inflammatory cytokine interleukin 10 (IL-10) by association with HDAC6.

    “Histone deacetylase 11 has been implicated in immune response cascades and shown to regulate the expression of the anti-inflammatory cytokine interleukin 10 (IL-10) by association with HDAC6 (Villagra et al., 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Villagra et al., 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data
    § Protein concentration assay

    HDAC11 relative purity was determined by coomassie-stained gel electrophoresis and used for the calculation of HDAC11 protein concentration in each stock solution.

    “HDAC11 relative purity was determined by coomasie-stained gel electrophoresis (Supplemental Fig. S2A) and used for the calculation of HDAC11 protein concentration in each Stock solution.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § DISCUSSION

    The hydroxamic acid-containing macrocyclic inhibitors TpxB Asuha and ApiA Asuha are not HDAC11-selective because they have been shown to potently inhibit several other members of the enzyme class.

    “Although these inhibitors are not HDAC11-selective as they have all been shown to potently inhibit several other members of the enzyme class (Kitir et al., 2017)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kitir et al., 2017 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § INTRODUCTION

    HDACs have been implicated in metabolism, inflammation, circadian rhythm, neurological development, and brain function.

    “HDACs have been implicated in diverse biology including metabolism, inflammation, circadian rhythm, as well as neurological development and brain function (Guan et al., 2009; Villagra et al., 2009; Gräff et al., 2012; Jakovcevski and Akbarian, 2012; Falkenberg and Johnstone, 2014; Tough et al., 2016).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Guan et al., 2009 source

      Not checked in the free run.

    • cites Villagra et al., 2009 source

      Not checked in the free run.

    • cites Gräff et al., 2012

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § DISCUSSION

    HDAC11 is involved in Fox3p+ T-regulatory cell function.

    “More recently, HDAC11 has also been shown to be involved on Fox3p+ T-regulatory cell function (Huang et al., 2017)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Huang et al., 2017 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given
    § Buffers used for in vitro enzymatic characterization

    All fluorescence-based HDAC deacylase activity assays were performed with duplicate series in each assay, and each assay was performed at least twice.

    “All fluorescence-based HDAC deacylase activity assays were performed in black low binding 96-well microtiter plates (Corning half-area wells), with duplicate series in each assay and each assay performed at least twice.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § INTRODUCTION

    Class III KDACs comprise the structurally and mechanistically distinct NAD+-dependent sirtuins (SIRT1-7).

    “Class III KDACs comprise the structurally and mechanistically distinct NAD + -dependent sirtuins (SIRT1-7) (Frye, 2000).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Frye, 2000 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Chemical synthesis

    Assignment of NMR spectra was based on correlation spectroscopy (COSY, HSQC, and HMBC spectra).

    “Assignment of NMR spectra are based on correlation spectroscopy (COSY, HSQC, and HMBC spectra).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation
    § Chemical synthesis

    Loading of resin during solid phase peptide synthesis was checked spectrophotometrically by quantifying the amount of Fmoc released upon cleavage of a small sample.

    “Loading of resin during solid phase peptide synthesis was checked spectrophotometrically, quantifying the amount of Fmoc released upon cleavage of a small sample.”
    Quote in the paperNot a substantial claim
28 of 28

  • The paper relies on this without support.

    HDAC11 is the least understood or least characterized isozyme of the human zinc-dependent HDACs.

    “the most recently discovered member, HDAC11, is the only member assigned to subclass IV, the smallest protein, and the least well understood with regards to biological function.”
    “but it remains the least understood isozyme of the class.”
    “Histone deacetylase 11 is the least characterized of the human zinc-dependent HDACs.”

  • The paper relies on this without support.

    Class IIa isoforms 4, 5, 7, and 9 as well as HDACs 10 and 11 exhibit low deacetylase activity in vitro.

    “several HDACs, i.e. class IIa isoforms 4, 5, 7, and 9 as well as HDACs 10 and 11, exhibit low deacetylase activity in vitro.”

  • The paper relies on this without support.

    Kmyr is a known physiologically relevant posttranslational modification.

    “the identified activity against lysine side chains modified with the 14-carbon atom myristic acid, which is a known PTM, was remarkably efficient for an HDAC enzyme.”

  • The authors state this as an assumption.

    A standard fast-on/fast-off mechanism applies to the inhibitor binding, so that IC50 values can be obtained by fitting the concentration-response equation with variable Hill slope.

    “assuming a standard fast-on/fast-off mechanism, IC50 values were obtained by fitting the resulting data to the concentration-response equation with variable Hill slope”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • HDAC11 shows strong activity toward long-chain acyl groups and plays a role in lipid metabolism.

    “HDAC11 shows strong activity toward long-chain acyl groups and plays a role in lipid metabolism (Moreno-Yruela et al., 2018; Kutil et al., 2018).”

    From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Moreno-Yruela et al., 2018

    The Introduction and the section ‘HDAC11 cleaves a narrow selection of long chain acyl groups’ report strong activity toward certain long-chain acyl modifications, particularly those with 12–14 carbons. The paper does not establish a role for HDAC11 in lipid metabolism; it says its biological function remains to be investigated (Significance; page numbers unavailable). (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Peptide 7 and 8 acylation assignments are reversed

    Minor

    The results identify peptide 7 as myristoylated and peptide 8 as acetylated, but the HPLC-MS methods assign Kac to 7 and Kmyr to 8. This reverses the identities of the substrates used to validate HDAC11's preference for demyristoylation.

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Authors
Moreno-Yruela, C., Galleano, I., Madsen, A. S., & Olsen, C. A.
Affiliations
University of Copenhagen (DK)
Corresponding author
Olsen, Christian A.
ORCID
Venue
Cell Chemical Biology
Publisher
Elsevier BV
Published
2018-07
Volume
25
Issue
7
Pages
849-856.e8
ISSN
  • 2451-9448 (ISSN-L)
  • 2451-9456
DOI
10.1016/j.chembiol.2018.04.007
OpenAlex
W2766615847
Cited by
149
References
61
Citations by year
2026: 14 · 2025: 22 · 2024: 17 · 2023: 24 · 2022: 14 · 2021: 17 · 2020: 19 · 2019: 17 · 2018: 5
FWCI
5.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell chemical biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • European Research Council (ERC-CoG-725172 – SIRFUNCT)
  • Københavns Universitet
  • Carlsbergfondet (2011_01_0169, 2013_01_0333, CF15-0115)
  • Novo Nordisk Fonden (NNF15OC0017334)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
HDAC11, histone deacetylase inhibitors, romidepsin, vorinostat, chemical probes
MeSH terms
Dose-Response Relationship, Drug, Histone Deacetylases, Humans, Hydrolases, Hydroxamic Acids, Peptides, Structure-Activity Relationship, Molecular Structure, Histone Deacetylase Inhibitors

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