HDAC8 catalyzes the hydrolysis of long chain fatty acyl lysine
Open accessAbstract
The histone deacetylase (HDAC) family regulates many biological pathways through the deacetylation of lysine residues on histone and nonhistone proteins. Mammals have 18 HDACs that are classified into four classes. Class I, II, and IV are zinc-dependent, while class III is nicotinamide adenine dinucleotide (NAD + )-dependent lysine deacetylase or sirtuins. HDAC8, a class I HDAC family member, has been shown to have low deacetylation activity compared to other HDACs in vitro. Recent studies showed that several sirtuins, with low deacetylase activities, can actually hydrolyze other acyl lysine modifications more efficiently. Inspired by this, we tested the activity of HDAC8 using a variety of different acyl lysine peptides. Screening a panel of peptides with different acyl lysine modifications, we found that HDAC8 can catalyze the removal of acyl groups with 2–16 carbons from lysine 9 of the histone H3 peptide (H3K9). Interestingly, the catalytic efficiencies ( k cat / K m ) of HDAC8 on octanoyl, dodecanoyl, and myristoyl lysine are several-fold better than that on acetyl lysine. The increased catalytic efficiencies of HDAC8 on larger fatty acyl groups are due to the much lower K m values. T-cell leukemia Jurkat cells treated with a HDAC8 specific inhibitor, PCI-34051, exhibited an increase in global fatty acylation compared to control treatment. Thus, the de-fatty-acylation activity of HDAC8 is likely physiologically relevant. This is the first report of a zinc-dependent HDAC with de-fatty-acylation activity, and identification of HDAC8 de-fatty-acylation targets will help to further understand the function of HDAC8 and protein lysine fatty acylation.
AI snapshot
Written from the paper’s full text.
TL;DR
HDAC8, a zinc-dependent class I HDAC, can hydrolyze long-chain fatty acyl groups from lysine residues, with higher catalytic efficiency on octanoyl-, dodecanoyl-, and myristoyl-H3K9 peptides than on acetyl-H3K9. Treatment of Jurkat cells with the HDAC8-specific inhibitor PCI-34051 increased global protein fatty acylation, suggesting this defatty-acylation activity is physiologically relevant.
Key findings
- HDAC8 removed acyl groups with 2–16 carbons from H3K9 peptides, including butyryl, octanoyl, dodecanoyl, myristoyl, and palmitoyl, but did not remove succinyl, malonyl, biotinyl, lipoyl, crotonyl, or 2-hydroxyisobutyryl groups from the peptides tested.
- HDAC8 catalytic efficiencies (kcat/Km) on octanoyl-, dodecanoyl-, and myristoyl-H3K9 were two to three times higher than on acetyl-H3K9; the myristoyl-H3K9 Km was approximately 16 μM, while the deacetylation Km could not be obtained because initial rates were linear with acetyl peptide concentrations used.
- HDAC8 expressed from Sf9 insect cells gave higher kcat/Km values for both deacetylation and demyristoylation than E. coli-expressed HDAC8, but demyristoylation catalytic efficiency remained >2 times higher than deacetylation.
- PCI-34051 and SAHA inhibited both demyristoylation and deacetylation in a dose-dependent manner; PCI-34051 inhibited both activities with ten times lower IC50 values than SAHA. In Jurkat cells, PCI-34051 treatment significantly increased global fatty acylation in a time- and dose-dependent manner, while SAHA, Panobinostat, and Mocetinostat did not.
Methods
- Recombinant human HDAC8 was overexpressed and purified from E. coli BL21 cells; commercial HDAC8 from Sf9 cells was also used for kinetics. Acyl peptides were synthesized by solid-phase peptide synthesis and verified by LC-MS.
- In vitro activity was measured by an HPLC-based assay using 25 μM acyl peptides and 1–5 μM HDAC8 at 37 °C for 1 hr; kinetics used varying substrate concentrations (e.g., 0–1,200 μM acetyl-H3K9, 0–100 μM myristoyl-H3K9) with 1 μM HDAC8. Inhibition assays pre-incubated HDAC8 with inhibitors before adding 25 μM substrate peptide.
- Metabolic labeling used Jurkat cells (1×10⁶ per flask) treated with 25 or 50 μM PCI-34051 or DMSO for 15 hrs, then 50 μM Alk12 or Alk14 for 6 hrs; labeled proteins were clicked to BODIPY-azide, treated with hydroxylamine, separated by SDS-PAGE, and visualized. Western blot was used to detect global lysine acetylation.
Limitations
- The paper states that the E. coli expression system for HDAC8 might have caused low activity due to lack of certain post-translational modifications; they addressed this partly by using Sf9-expressed HDAC8.
- The paper states that only two direct HDAC8 targets, ERRα and SMC3, have been substantially validated, and that identification of additional HDAC8 defatty-acylation targets is needed to understand its physiological role.
- Evident from the text: the cellular evidence relies on a global fatty acylation labeling assay and an HDAC8 inhibitor, so specific endogenous defatty-acylation substrates were not identified; the significant increase was seen in Jurkat cells, while HeLa, HEK-293T, and MDA-MB-231 cells showed only slightly increased fatty acylation.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 of 25 cited sources checked · 0 supported · 0 flagged
- Findingown data
PCI-34051 inhibited the deacylase activity of HDAC8 on both acetyl- and myristoyl-H3K9 peptides with comparable potency.
“Notably, PCI-34051 inhibited the deacylase activity of HDAC8 on both the acetyl- and myristoyl-H3K9 peptides with comparable potency.”
Quote in the paperSubstantial claim - Findingown data
HDAC8 expressed from Sf9 insect cells gave higher kcat/Km values for both deacetylation and demyristoylation than HDAC8 expressed from E. coli.
“Indeed, we obtained higher kcat/Km values for both deacetylation and demyristoylation from HDAC8 expressed from Sf9 insect cells.”
Quote in the paperNot a substantial claim - Findingown data
None of the N-terminal glycine myristoylated peptides tested were HDAC8 substrates.
“However, none of the N-terminal glycine myristoylated peptides were HDAC8 substrates (Table 1 and Supplementary Fig. S1).”
Quote in the paperNot a substantial claim - Findingown data
HDAC8 can catalyze the removal of long chain fatty-acyl groups from different peptide backbone sequences.
“We have found that HDAC8 can catalyze the removal of long chain fatty-acyl groups from different peptide backbone sequences.”
Quote in the paperSubstantial claim - Findingown data
For HDAC8 purified from Sf9 insect cells, demyristoylation catalytic efficiency remained >2 times higher than deacetylation.
“Although the HDAC8 purified from insect cells gave much higher activity, the demyristoylation catalytic efficiency remained >2 times higher than that of deacetylation.”
Quote in the paperSubstantial claim
- Findingown data
Among the HDAC inhibitors tested, only PCI-34051-treated Jurkat cells exhibited enhanced global protein lysine fatty acylation.
“As we expected, only PCI-34051-treated Jurkat cells exhibited enhanced global protein lysine fatty acylation (Fig. 4D).”
Quote in the paperSubstantial claim - Findingown data
The global fatty acylation labeling signal from cells treated with SAHA and Panobinostat was much lower than the control.
“Notably, the global fatty acylation labeling signal (measured by Alk12 labeling) from the cells treated with SAHA and Panobinostat was much lower than the control.”
Quote in the paperSubstantial claim - Findingown data
Similar results were obtained when Alk14, a palmitic acid analogue, was used as a metabolic labeling probe.
“Moreover, similar results were obtained when we used Alk14, a palmitic acid analogue, as a metabolic labeling probe (Supplementary Fig. S5C).”
Quote in the paperNot a substantial claim - Findingown data
Treatment of Jurkat cells with PCI-34051 significantly increased the fatty acylation level.
“T-cell leukemia Jurkat cells treated with a HDAC8 specific inhibitor, PCI-34051, exhibited an increase in global fatty acylation compared to control treatment.”
- Also stated in: § Effect of the HDAC8 specific inhibitor (PCI-34051) on global fatty acylation level in mammalian cells · plain
“In contrast, the treatment of T lymphocyte Jurkat cells with PCI-34051 significantly increased the fatty acylation level (Fig. 4C).”
Quote in the paperSubstantial claim- Rests on an assumption: PCI-34051 specifically inhibits HDAC8 in Jurkat cells at the concentrations used, so the observed increase in global fatty acylation is due to HDAC8 inhibition.
- Also stated in: § Effect of the HDAC8 specific inhibitor (PCI-34051) on global fatty acylation level in mammalian cells · plain
- Findingown data
Both demyristoylation and deacetylation activities of HDAC8 were inhibited by PCI-34051 and SAHA in a dose-response manner.
“As shown in Figure 3, both the demyristoylation and deacetylation activities of HDAC8 were inhibited by the two inhibitors in a dose response manner.”
Quote in the paperSubstantial claim - Findingown data
HeLa, HEK-293T, and MDA-MB 231 cells treated with PCI-34051 showed slightly increased fatty acylation compared to DMSO control.
“We found that HeLa, HEK-293T, and MDA-MB 231 cells treated with PCI-34051 showed slightly increased fatty acylation compared to the control that was treated with DMSO (Supplementary Fig. S4).”
Quote in the paperSubstantial claim - Findingown data
HDAC8 could not remove negatively charged succinyl or malonyl groups from H3K9 peptides.
“However, HDAC8 could not remove the negatively charged succinyl or malonyl groups from H3K9 peptides.”
Quote in the paperSubstantial claim - Findingown data
HDAC8 catalytic efficiencies (kcat/Km) on octanoyl-, dodecanoyl-, and myristoyl-H3K9 peptides are higher than on acetyl-H3K9 peptide.
“Interestingly, the catalytic efficiencies (kcat/Km) of HDAC8 on octanoyl, dodecanoyl, and myristoyl lysine are several folds better than that on acetyl lysine.”
- Also stated in: § HDAC8 can remove long chain fatty acyl groups in vitro · plain
“The HDAC8 catalytic efficiencies (kcat/Km values) on the longer fatty acyl groups, octanoyl-, dodecanoyl-, and myristoyl-H3K9, are two to three times higher than that on the acetyl peptide.”
Quote in the paperSubstantial claim - Also stated in: § HDAC8 can remove long chain fatty acyl groups in vitro · plain
- Findingown data
HDAC8 could not remove 2-hydroxyisobutyryl groups from any of the peptides tested.
“Similarly, HDAC8 could not remove 2-hydroxyisobutyryl groups from any of the peptides tested (Table 1 and Supplementary Fig. S1).”
Quote in the paperSubstantial claim - Findingown data
PCI-34051 inhibited both catalytic activities with ten times lower IC50 values compared to SAHA.
“PCI-34051 was able to inhibit both catalytic activities with ten times lower IC50 values compared to SAHA (Table 3).”
Quote in the paperSubstantial claim - Findingown data
The Km value for the myristoyl H3K9 peptide was approximately 16 μM.
“In contrast, the Km value for the myristoyl H3K9 peptide was approximately 16 μM.”
Quote in the paperNot a substantial claim - Findingown data
The bulkier biotinyl and lipoyl groups were not good HDAC8 substrates.
“The bulkier biotinyl and lipoyl groups were also not good HDAC8 substrates (Table 1 and Supplementary Fig. S1).”
Quote in the paperNot a substantial claim - Findingown data
The increase in protein fatty acylation in Jurkat cells treated with PCI-34051 was time- and dose-dependent.
“The increase in protein fatty acylation was time- and dose-dependent (Fig. 4C, Supplementary Fig. S5A and S5B).”
Quote in the paperSubstantial claim - Interpretationreasoning
This is the first report of a zinc-dependent HDAC with defatty-acylation activity.
“While some of the sirtuins, the NAD+-dependent HDACs, have been recognized as protein defatty-acylases,12,16,17 this is the first report of a zinc-dependent HDAC possessing this enzymatic activity.”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationown data
The increased catalytic efficiencies of HDAC8 on larger fatty acyl groups are due to much lower Km values.
“The increased catalytic efficiencies of HDAC8 on larger fatty acyl groups are due to the much lower Km values.”
- Also stated in: § Effect of the HDAC8 specific inhibitor (PCI-34051) on global fatty acylation level in mammalian cells · plain
“The myristoyl peptide has a much lower Km values compared to the acetyl peptide leading to a higher catalytic efficiency of demyristoylation over deacetylation.”
Quote in the paperSubstantial claim - Also stated in: § Effect of the HDAC8 specific inhibitor (PCI-34051) on global fatty acylation level in mammalian cells · plain
- Premisecitation
The region around the binding pocket of HDAC8 has been suggested to be conformationally flexible.
“This region has been suggested to be conformational flexible, and this property might allow HDAC8 to accommodate different substrates.31”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] source
Not checked in the free run.
- Premisecitation
The complexes between HDAC8 and inhibitors displayed structural variation on the surface of HDAC8 around the binding pocket.
“Interestingly, the complexes between HDAC8 and the inhibitors displayed structural variation on the surface of HDAC8 around the binding pocket.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] source
Not checked in the free run.
- Interpretationown data
HDAC8 enzymatic activity is dependent on the peptide sequence.
“Therefore, HDAC8 enzymatic activity is dependent on the peptide sequence.”
Quote in the paperSubstantial claim - Interpretationown data
The defatty-acylation activity of HDAC8 is likely physiologically relevant.
“Thus, the defatty-acylation activity of HDAC8 is likely physiologically relevant.”
- Also stated in: § Effect of the HDAC8 specific inhibitor (PCI-34051) on global fatty acylation level in mammalian cells · hedged
“These results suggest that HDAC8 lysine defatty-acylation is likely physiologically relevant.”
Quote in the paperSubstantial claim- Rests on an assumption: PCI-34051 specifically inhibits HDAC8 in Jurkat cells at the concentrations used, so the observed increase in global fatty acylation is due to HDAC8 inhibition.
- Also stated in: § Effect of the HDAC8 specific inhibitor (PCI-34051) on global fatty acylation level in mammalian cells · hedged
- Premisecitation
Previous kinetics studies show that all HDACs have Km values between 20-40 μM, except HDAC8 which has a significantly higher Km (>200 μM).
“Previous kinetics studies of different HDACs (HDAC1, 2, 3, 6, 8 and 10)11 show that all of the HDACs have Km values between 20-40 μM, except for HDAC8 which has a significantly higher Km (>200 μM).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] source
Not checked in the free run.
- Premisecitation
Only two direct HDAC8 targets, ERRα and SMC3, have been substantially validated.
“However, so far, only two proteins have been validated as HDAC8 deacetylation targets, estrogen-related receptor alpha (ERRα)9 and structural maintenance of chromosomes protein 3 (SMC3).10”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
HDAC8 has the lowest kcat/Km value on acetyl lysine peptides (~60±7 M−1S−1) when compared to other HDACs tested.
“Overall, HDAC8 has lowest kcat/Km value on acetyl lysine peptides (~60±7 M−1S−1) when compared to other HDACs tested.11”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] source
Not checked in the free run.
- May combine two claims. 7
- Classified as probably not a substantial claim. 12
- The quote only partly states this claim. 1
May combine two claims.
Findingown dataSAHA and Panobinostat predominantly increased acetylation of protein bands around 55 kDa, while PCI-34051 and Mocetinostat did not noticeably increase protein lysine acetylation.
“We also detected the global lysine acetylation level by Western blot, and found that SAHA and Panobinostat predominantly increased the acetylation of protein bands around 55 kDa, while PCI-34051 and Mocetinostat did not noticeably increase protein lysine acetylation (Fig. 4E).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataHDAC8 could remove acetyl groups, but not crotonyl groups, from H2AK119 and H3K56 peptides.
“HDAC8 could remove acetyl groups, but not crotonyl groups from both the H2AK119 and H3K56 peptides (Table 1 and Supplementary Fig. S1).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataFor deacetylation, Km values could not be obtained because the initial reaction rate was linear with the acetyl peptide concentrations used.
“For deacetylation, we could not obtain the Km values as the initial reaction rate was linear with the acetyl peptide concentrations we used.”
Quote in the paperNot a substantial claimMay combine two claims. The quote only partly states this claim.
Findingown dataHDAC8 can catalyze the removal of acyl groups with 2-16 carbons from lysine 9 of the histone H3 peptide (H3K9), including efficient deoctanoylation, dedodecanoylation, and demyristoylation.
“Screening a panel of peptides with different acyl lysine modifications, we found that HDAC8 can catalyze the removal of acyl groups with 2-16 carbons from lysine 9 of the histone H3 peptide (H3K9).”
- Also stated in: § HDAC8 can remove long chain fatty acyl groups in vitro · hedged
“Using an HPLC-based assay, we found HDAC8 could remove both acetyl and several larger acyl groups (butyryl, octanoyl, dodecanoyl, myristoyl, and palmitoyl) from the lysine residue of H3K9 peptides (Table 1 and Fig. 1).”
- Also stated in: § Effect of the HDAC8 specific inhibitor (PCI-34051) on global fatty acylation level in mammalian cells · boosted
“We showed here that HDAC8 can efficiently catalyze defatty-acylation, including deoctanoylation, dedodecanoylation, and demyristoylation.”
Quote in the paperSubstantial claim- Also stated in: § HDAC8 can remove long chain fatty acyl groups in vitro · hedged
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationProtein fatty acylation plays an essential role in cell signaling, membrane trafficking, protein-membrane interactions, and cellular localization.
“Protein fatty acylation has been known to play an essential role in cell signaling, membrane trafficking, protein-membrane interactions, and cellular localization.33”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [33] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCrystal structures of human HDAC8 in complex with different inhibitors revealed a single α/β-domain with a core eight-stranded parallel β-sheet and 11 α-helices.
“Crystal structures of human HDAC8, in complex with different inhibitors, have been reported; they revealed a single α/β-domain with a core eight-stranded parallel β-sheet and 11 α-helices.7, 31, 32”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe majority of fatty-acylated proteins have N-glycine myristoylation or S-palmitoylation, while only a few proteins have lysine fatty acylation.
“The majority of these fatty-acylated proteins have been reported to have N-glycine myristoylation or S-palmitoylation, while only a few proteins are reported to have lysine fatty acylation.15,34”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSeveral NAD+-dependent deacetylases, SIRT1, SIRT2, SIRT3 and SIRT6, have been previously reported to possess lysine defatty-acylation activities.
“Several NAD+-dependent deacetylase, SIRT1, SIRT2, SIRT3 and SIRT6, have been previously reported to possess lysine defatty-acylation activities.15-17”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSIRT1, 2, 3 and SIRT6 are capable of hydrolyzing long chain fatty acyl groups from lysine residues.
“and SIRT1, 2, 3 and SIRT6 are capable of hydrolyzing long chain fatty acyl groups from lysine residues.15-17”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationSIRT5 exhibits efficient activity to lysine desuccinylation, demalonylation and glutarylation.
“For example, SIRT5 exhibits efficient activity to lysine desuccinylation, demalonylation and glutarylation12-14”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningThe identification of an additional enzyme with lysine defatty-acylation activity suggests that lysine fatty acylation might be a more abundant modification than previously recognized, and it may play important roles in biology.
“The identification of an additional enzyme with lysine defatty-acylation activity suggests that lysine fatty acylation might be a more abundant modification than previously recognized, and it may play important roles in biology.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataHDAC8 fractions with greater than 80% purity were pooled for experiments.
“The fractions containing HDAC8 with greater than 80% purity were pooled and concentrated using an Amicon Ultra-0.5 mL 10 kDa concentrator (EMD Millipore) and subsequently aliquoted into small volumes and stored at −80 °C.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenEach kinetics reaction was performed in duplicate to ensure reproducibility.
“Each reaction was performed in duplicate to ensure reproducibility.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductown dataProduct formation was verified by LC-MS.
“The product formation was verified by LC-MS (LCQ Fleet, Thermo Scientific).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationClass I, II, and IV HDACs are zinc-dependent while class III is NAD+-dependent.
“Class I, II, and IV are zinc-dependent while class III is nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacetylase or sirtuins.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe synthesized acyl peptides were verified using LC-MS.
“The synthesized peptides were verified using LC-MS (LCQ Fleet, Thermo Scientific).”
Quote in the paperNot a substantial claim
The paper relies on this without support.
PCI-34051 specifically inhibits HDAC8 in Jurkat cells at the concentrations used, so the observed increase in global fatty acylation is due to HDAC8 inhibition.
“Since PCI-34051 can efficiently inhibit HDAC8 demyristoylation in vitro, we hypothesized that if the HDAC8 defatty-acylation activity is physiologically relevant, treating cells with PCI-34051 should increase protein lysine fatty-acylation level.”
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?
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).”
From Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase (2018) · cites this paper as Aramsangtienchai et al., 2016
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Jiang, H. X., Khan, S., Wang, Y., Charron, G., He, B., Sebastián, C., Du, J., Kim, R., Ge, E. J., Mostoslavsky, R., et al. (2013) · Nature · doi:10.2210/pdb3zg6/pdb · Cited by 169 · see citing works
Self-citationScuto, A., Kirschbaum, M., Kowolik, C., Kretzner, L., Juhasz, A., Atadja, P., Pullarkat, V., Bhatia, R., Forman, S., Yen, Y., et al. (2008) · Blood · doi:10.1182/blood-2007-10-117762 · Cited by 141 · see citing works
Myristyl acylation of the tumor necrosis factor alpha precursor on specific lysine residues.
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Kinetics and Comparative Reactivity of Human Class I and Class IIb Histone Deacetylases
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Plasmodium falciparum Sir2A Preferentially Hydrolyzes Medium and Long Chain Fatty Acyl Lysine
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Flagged first, then by citations
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Sorted by citations
HDAC11 regulates type I interferon signaling through defatty-acylation of SHMT2
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Self-citationHistone deacetylase 11 is a fatty-acid deacylase
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Structure, mechanism, and inhibition of the zinc-dependent histone deacetylases
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Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase
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Role of histone deacetylases and their inhibitors in neurological diseases
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HDACs and the epigenetic plasticity of cancer cells: target the complexity
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HDAC8 functions in spindle assembly during mouse oocyte meiosis
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Baselious, F., Robaa, D., & Sippl, W. (2023) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2023.107700 · Cited by 20 · see citing works
- Authors
- Aramsangtienchai, P., Spiegelman, N. A., He, B., Miller, S. P., Dai, L., Zhao, Y., & Lin, H.
- Affiliations
- Cornell University (US)
- University of Chicago (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Lin, Hening
- ORCID
- Venue
- ACS Chemical Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-08-05
- Volume
- 11
- Issue
- 10
- Pages
- 2685-2692
- ISSN
- 1554-8929 (ISSN-L)
- 1554-8937
- PMC
- PMC5305809
- OpenAlex
- W2476113726
- Semantic Scholar
- 88002fa6cea2cd9cca87b699e04c670b0a7a9aef
- Cited by
- 118
- References
- 36
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 18 · 2023: 8 · 2022: 13 · 2021: 13 · 2020: 12 · 2019: 14 · 2018: 8 · 2017: 8 · 2016: 1
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- ACS Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services (DK107868, GM098596, GM105933, GM115961)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- HDAC8, histone deacetylase, lysine acylation, H3K9, catalytic efficiency, Jurkat cells
- MeSH terms
- Amino Acid Sequence, Fatty Acids, Histone Deacetylases, Hydrolysis, Lysine, Repressor Proteins, Biocatalysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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