Dephosphorylation at a Conserved SP Motif Governs cAMP Sensitivity and Nuclear Localization of Class IIa Histone Deacetylases*

Walkinshaw, Donald R.; Weist, Ryan; Xiao, Lin; Kou, Yan; Kim, Go-Woon; Yang, Xiang-Jiao

doi:10.1074/jbc.m112.445668

Cited by 22 publications

(24 citation statements)

References 89 publications

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“…After cooling down for 20 min, the sections were circled with a PAP pen (Invitrogen, 00-8877) and rinsed with PBS three times for 5 min each. The remaining fluorescence microscopic analysis was similar to that used for cultured cells (63). After permeabilization with a few drops of the immunofluorescence (IF) buffer (PBS, 0.2% Triton X-100, and 0.05% Tween 20) for 30 min, the sections were incubated with drops of the IF blocking solution (IF buffer containing 2% bovine serum albumin) for 1 h. Then the anti-␣-tubulin antibody (diluted at 1:500) or the anti-acetylated ␣-tubulin antibody (the 6-11b-1 clone, diluted to 1:1000) was added, and the incubation was carried out at room temperature for 3 h or overnight at 4°C, with gentle agitation.…”

Section: Animals-three Atat1mentioning

confidence: 99%

Mice Lacking α-Tubulin Acetyltransferase 1 Are Viable but Display α-Tubulin Acetylation Deficiency and Dentate Gyrus Distortion

Kim

Ghorbani

et al. 2013

Journal of Biological Chemistry

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Background: Biological functions of mammalian Atat1 and its contribution to ␣-tubulin acetylation in vivo remain elusive. Results: Atat1-null mice are viable but possess deficient ␣-tubulin acetylation and a bulge in the dentate gyrus. Conclusion: Mouse Atat1 is a predominant ␣-tubulin acetyltransferase in vivo and fine-tunes hippocampus development. Significance: Mammalian Atat1 is not required for survival and development but may regulate more advanced functions.

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Section: Animals-three Atat1mentioning

confidence: 99%

Mice Lacking α-Tubulin Acetyltransferase 1 Are Viable but Display α-Tubulin Acetylation Deficiency and Dentate Gyrus Distortion

Kim

Ghorbani

et al. 2013

Journal of Biological Chemistry

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120

100

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“…To investigate the effects of β‐AR stimulation on the phosphorylation status of HDAC5 at S279, we made use of a recently described rabbit polyclonal antibody that detects phosphorylation of the conserved serine residue (S266) in HDAC4 . As the phospho‐peptide sequence used to generate the anti‐pS266 HDAC4 antibody shares 100% amino acid identity with the pS279 motif in HDAC5 (Figure A), we predicted that this antibody would cross‐react with phosphorylated S279 in HDAC5.…”

Section: Resultsmentioning

confidence: 99%

β‐Adrenergic Stimulation Induces Histone Deacetylase 5 (HDAC5) Nuclear Accumulation in Cardiomyocytes by B55α‐PP2A‐Mediated Dephosphorylation

Weeks

Ranieri

Karaś

et al. 2017

JAHA

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BackgroundClass IIa histone deacetylase (HDAC) isoforms such as HDAC5 are critical signal‐responsive repressors of maladaptive cardiomyocyte hypertrophy, through nuclear interactions with transcription factors including myocyte enhancer factor‐2. β‐Adrenoceptor (β‐AR) stimulation, a signal of fundamental importance in regulating cardiac function, has been proposed to induce both phosphorylation‐independent nuclear export and phosphorylation‐dependent nuclear accumulation of cardiomyocyte HDAC5. The relative importance of phosphorylation at Ser259/Ser498 versus Ser279 in HDAC5 regulation is also controversial. We aimed to determine the impact of β‐AR stimulation on the phosphorylation, localization, and function of cardiomyocyte HDAC5 and delineate underlying molecular mechanisms.Methods and ResultsA novel 3‐dimensional confocal microscopy method that objectively quantifies the whole‐cell nuclear/cytoplasmic distribution of green fluorescent protein tagged HDAC5 revealed the β‐AR agonist isoproterenol to induce β1‐AR‐mediated and protein kinase A‐dependent HDAC5 nuclear accumulation in adult rat cardiomyocytes, which was accompanied by dephosphorylation at Ser259/279/498. Mutation of Ser259/Ser498 to Ala promoted HDAC5 nuclear accumulation and myocyte enhancer factor‐2 inhibition, whereas Ser279 ablation had no such effect and did not block isoproterenol‐induced nuclear accumulation. Inhibition of the Ser/Thr phosphatase PP2A blocked isoproterenol‐induced HDAC5 dephosphorylation. Co‐immunoprecipitation revealed a specific interaction of HDAC5 with the PP2A targeting subunit B55α, as well as catalytic and scaffolding subunits, which increased >3‐fold with isoproterenol. Knockdown of B55α in neonatal cardiomyocytes attenuated isoproterenol‐induced HDAC5 dephosphorylation.Conclusionsβ‐AR stimulation induces HDAC5 nuclear accumulation in cardiomyocytes by a mechanism that is protein kinase A‐dependent but requires B55α‐PP2A‐mediated dephosphorylation of Ser259/Ser498 rather than protein kinase A‐mediated phosphorylation of Ser279.

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“…Western blot analysis was performed as described [25,26]. Briefly, cells were washed two times with PBS and lysed in buffer K (20 mM sodium phosphate, pH 7.0, 150 mM KCl, 30 mM sodium pyrophosphate, 0.1% Nonidet P40, 5 mM EDTA, 10 mM NaF, 0.1 mM Na 3 VO 4 , and protease inhibitors).…”

Section: Immunoblottingmentioning

confidence: 99%

The SUMO Conjugating Enzyme Ubc9 Is Required for Inducing and Maintaining Stem Cell Pluripotency

et al. 2014

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Sumoylation adds a small ubiquitin-like modifier (SUMO) polypeptide to the e-amino group of a lysine residue. Reminiscent of ubiquitination, sumoylation is catalyzed by an enzymatic cascade composed of E1, E2, and E3. For sumoylation, this cascade uses Ubc9 (ubiquitin conjugating enzyme 9, now officially named ubiquitin conjugating enzyme E2I [UBE2I]) as the sole E2 enzyme. Here, we report that expression of endogenous Ubc9 increases during reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem (iPS) cells. In addition, this E2 enzyme is required for reprogramming as its suppression dramatically inhibits iPS cell induction. While Ubc9 knockdown does not affect survival of MEFs and immortalized fibroblasts, Ubc9 is essential for embryonic stem cell (ESC) survival. In addition, we have found that Ubc9 knockdown stimulates apoptosis in ESCs but not in MEFs. Furthermore, the knockdown decreases the expression of the well-known pluripotency marker Nanog and the classical reprogramming factors Klf4, Oct4, and Sox2 in ESCs. Together, these observations indicate that while dispensable for fibroblast survival, the sole SUMO E2 enzyme Ubc9 plays a critical role in reprogramming fibroblasts to iPS cells and maintaining ESC pluripotency. STEM CELLS

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Dephosphorylation at a Conserved SP Motif Governs cAMP Sensitivity and Nuclear Localization of Class IIa Histone Deacetylases*

Cited by 22 publications

References 89 publications

Mice Lacking α-Tubulin Acetyltransferase 1 Are Viable but Display α-Tubulin Acetylation Deficiency and Dentate Gyrus Distortion

Mice Lacking α-Tubulin Acetyltransferase 1 Are Viable but Display α-Tubulin Acetylation Deficiency and Dentate Gyrus Distortion

β‐Adrenergic Stimulation Induces Histone Deacetylase 5 (HDAC5) Nuclear Accumulation in Cardiomyocytes by B55α‐PP2A‐Mediated Dephosphorylation

The SUMO Conjugating Enzyme Ubc9 Is Required for Inducing and Maintaining Stem Cell Pluripotency

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