Редактирование: HDAC5

Histone deacetylase 5 (EC 3.5.1.98) (HD5) (Antigen NY-CO-9) [KIAA0600]

==Publications==

{{medline-entry
|title=SENEBLOC, a long non-coding RNA suppresses senescence via p53-dependent and independent mechanisms.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32030426
|abstract=Long non-coding RNAs (lncRNAs) have emerged as important biological tuners. Here, we reveal the role of an uncharacterized lncRNA we call SENEBLOC that is expressed by both normal and transformed cells under homeostatic conditions. SENEBLOC was shown to block the induction of cellular senescence through dual mechanisms that converge to repress the expression of p21. SENEBLOC facilitates the association of p53 with [[MDM2]] by acting as a scaffold to promote p53 turnover and decrease p21 transactivation. Alternatively, SENEBLOC was shown to affect epigenetic silencing of the p21 gene promoter through regulation of [[HDAC5]]. Thus SENEBLOC drives both p53-dependent and p53-independent mechanisms that contribute to p21 repression. Moreover, SENEBLOC was shown to be involved in both oncogenic and replicative senescence, and from the perspective of senolytic agents we show that the antagonistic actions of rapamycin on senescence are dependent on SENEBLOC expression.
|mesh-terms=* Aging
* Animals
* Carcinogenesis
* Cyclin-Dependent Kinase Inhibitor p21
* Gene Expression Regulation, Neoplastic
* HCT116 Cells
* Heterografts
* Histone Deacetylases
* Humans
* Mice
* Neoplasms
* Protein Binding
* RNA, Long Noncoding
* Signal Transduction
* Tumor Suppressor Protein p53

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102969
}}
{{medline-entry
|title=Emerging roles for histone deacetylases in age-related muscle atrophy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28035339
|abstract= Skeletal muscle atrophy during aging, a process known as sarcopenia, is associated with muscle weakness, frailty, and the loss of independence in older adults. The mechanisms contributing to sarcopenia are not totally understood, but muscle fiber loss due to apoptosis, reduced stimulation of anabolic pathways, activation of catabolic pathways, denervation, and altered metabolism have been observed in muscle from old rodents and humans.   Recently, histone deacetylases (HDACs) have been implicated in muscle atrophy and dysfunction due to denervation, muscular dystrophy, and disuse, and HDACs play key roles in regulating metabolism in skeletal muscle. In this review, we will discuss the role of HDACs in muscle atrophy and the potential of HDAC inhibitors for the treatment of sarcopenia.   Several HDAC isoforms are potential targets for intervention in sarcopenia. Inhibition of [[HDAC1]] prevents muscle atrophy due to nutrient deprivation. [[HDAC3]] regulates metabolism in skeletal muscle and may inhibit oxidative metabolism during aging. [[HDAC4]] and [[HDAC5]] have been implicated in muscle atrophy due to denervation, a process implicated in sarcopenia. HDAC inhibitors are already in use in the clinic, and there is promise in targeting HDACs for the treatment of sarcopenia.

|keywords=* Aging
* epigenetics
* histone deacetylases
* sarcopenia
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166515
}}
{{medline-entry
|title=AMPK and HIF signaling pathways regulate both longevity and cancer growth: the good news and the bad news about survival mechanisms.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27259535
|abstract=The AMP-activated protein kinase (AMPK) and hypoxia-inducible factor (HIF) signaling pathways are evolutionarily-conserved survival mechanisms responding to two fundamental stresses, energy deficiency and/or oxygen deprivation. The AMPK and HIF pathways regulate the function of a survival network with several transcription factors, e.g. FOXO, NF-κB, NRF2, and p53, as well as with protein kinases and other factors, such as mTOR, [[ULK1]], [[HDAC5]], and [[SIRT1]]. Given that AMPK and HIF activation can enhance not only healthspan and lifespan but also cancer growth in a context-dependent manner; it seems that cancer cells can hijack certain survival factors to maintain their growth in harsh conditions. AMPK activation improves energy metabolism, stimulates autophagy, and inhibits inflammation, whereas HIF-1α increases angiogenesis and helps cells to adapt to severe conditions. First we will review how AMPK and HIF signaling mechanisms control the function of an integrated survival network which is able not only to improve the regulation of longevity but also support the progression of tumorigenesis. We will also describe distinct crossroads between the regulation of longevity and cancer, e.g. specific regulation through the AMPKα and HIF-α isoforms, the Warburg effect, mitochondrial dynamics, and cellular senescence.
|mesh-terms=* Age Distribution
* Aging
* Apoptosis
* Cell Proliferation
* Gene Expression Regulation, Neoplastic
* Humans
* Hypoxia-Inducible Factor 1, alpha Subunit
* Longevity
* Neoplasms
* Prevalence
* Protein Kinases
* Signal Transduction
* Survival Rate
|keywords=* Ageing
* Healthspan
* Lifespan
* Senescence
* Tumorigenesis
|full-text-url=https://sci-hub.do/10.1007/s10522-016-9655-7
}}
{{medline-entry
|title=AMPK/Snf1 signaling regulates histone acetylation: Impact on gene expression and epigenetic functions.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27010499
|abstract=AMP-activated protein kinase (AMPK) and its yeast homolog, Snf1, are critical regulators in the maintenance of energy metabolic balance not only stimulating energy production but also inhibiting energy-consuming processes. The AMPK/Snf1 signaling controls energy metabolism by specific phosphorylation of many metabolic enzymes and transcription factors, enhancing or suppressing their functions. The AMPK/Snf1 complexes can be translocated from cytoplasm into nuclei where they are involved in the regulation of transcription. Recent studies have indicated that AMPK/Snf1 activation can control histone acetylation through different mechanisms affecting not only gene transcription but also many other epigenetic functions. For instance, AMPK/Snf1 enzymes can phosphorylate the histone H3S10 (yeast) and H2BS36 (mammalian) sites which activate specific histone acetyltransferases (HAT), consequently enhancing histone acetylation. Moreover, nuclear AMPK can phosphorylate type 2A histone deacetylases (HDAC), e.g. [[HDAC4]] and [[HDAC5]], triggering their export from nuclei thus promoting histone acetylation reactions. AMPK activation can also increase the level of acetyl CoA, e.g. by inhibiting fatty acid and cholesterol syntheses. Acetyl CoA is a substrate for HATs, thus increasing their capacity for histone acetylation. On the other hand, AMPK can stimulate the activity of nicotinamide phosphoribosyltransferase (NAMPT) which increases the level of NAD( ). NAD( ) is a substrate for nuclear sirtuins, especially for [[SIRT1]] and [[SIRT6]], which deacetylate histones and transcription factors, e.g. those regulating ribosome synthesis and circadian clocks. Histone acetylation is an important epigenetic modification which subsequently can affect chromatin remodeling, e.g. via bromodomain proteins. We will review the signaling mechanisms of AMPK/Snf1 in the control of histone acetylation and subsequently clarify their role in the epigenetic regulation of ribosome synthesis and circadian clocks.
|mesh-terms=* AMP-Activated Protein Kinases
* Acetylation
* Animals
* Epigenesis, Genetic
* Histones
* Humans
* Protein-Serine-Threonine Kinases
* Signal Transduction
|keywords=* AMPK/Snf1
* Acetyl CoA
* Aging
* Chromatin
* Epigenetic
* Histone acetylation
|full-text-url=https://sci-hub.do/10.1016/j.cellsig.2016.03.009
}}