HDAC6 Regulates Radiosensitivity of Non-Small Cell Lung Cancer by Promoting Degradation of Chk1.

Abstract:

:We have previously discovered that HDAC6 regulates the DNA damage response (DDR) via modulating the homeostasis of a DNA mismatch repair protein, MSH2, through HDAC6's ubiquitin E3 ligase activity. Here, we have reported HDAC6's second potential E3 ligase substrate, a critical cell cycle checkpoint protein, Chk1. We have found that HDAC6 and Chk1 directly interact, and that HDAC6 ubiquitinates Chk1 in vivo and in vitro. Specifically, HDAC6 interacts with Chk1 via the DAC1 domain, which contains its ubiquitin E3 ligase activity. During the cell cycle, Chk1 protein levels fluctuate, peaking at the G2 phase, subsequently resolving via the ubiquitin-proteasome pathway, and thereby allowing cells to progress to the M phase. However, in HDAC6 knockdown non-small cell lung cancer (NSCLC) cells, Chk1 is constitutively active and fails to resolve post-ionizing radiation (IR), and this enhanced Chk1 activity leads to preferential G2 arrest in HDAC6 knockdown cells accompanied by a reduction in colony formation capacity and viability. Depletion or pharmacological inhibition of Chk1 in HDAC6 knockdown cells reverses this radiosensitive phenotype, suggesting that the radiosensitivity of HDAC6 knockdown cells is dependent on increased Chk1 kinase activity. Overall, our results highlight a novel mechanism of Chk1 regulation at the post-translational level, and a possible strategy for sensitizing NSCLC to radiation via inhibiting HDAC6's E3 ligase activity.

journal_name

Cells

journal_title

Cells

authors

Moses N,Zhang M,Wu JY,Hu C,Xiang S,Geng X,Chen Y,Bai W,Zhang YW,Bepler G,Zhang XM

doi

10.3390/cells9102237

subject

Has Abstract

pub_date

2020-10-04 00:00:00

issue

10

issn

2073-4409

pii

cells9102237

journal_volume

9

pub_type

杂志文章

相关文献

Cells文献大全
  • Fine-Tuning the Tumour Microenvironment: Current Perspectives on the Mechanisms of Tumour Immunosuppression.

    abstract::Immunotherapy has revolutionised the treatment of cancers by harnessing the power of the immune system to eradicate malignant tissue. However, it is well recognised that some cancers are highly resistant to these therapies, which is in part attributed to the immunosuppressive landscape of the tumour microenvironment (...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells10010056

    authors: Armitage JD,Newnes HV,McDonnell A,Bosco A,Waithman J

    更新日期:2021-01-01 00:00:00

  • Corticosterone Induces HMGB1 Release in Primary Cultured Rat Cortical Astrocytes: Involvement of Pannexin-1 and P2X7 Receptor-Dependent Mechanisms.

    abstract::A major risk factor for major depressive disorder (MDD) is stress. Stress leads to the release of high-mobility group box-1 (HMGB1), which in turn leads to neuroinflammation, a potential pathophysiological basis of MDD. The mechanism underlying stress-induced HMGB1 release is not known, but stress-associated glucocort...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9051068

    authors: Hisaoka-Nakashima K,Azuma H,Ishikawa F,Nakamura Y,Wang D,Liu K,Wake H,Nishibori M,Nakata Y,Morioka N

    更新日期:2020-04-25 00:00:00

  • Reappraisal of Human HOG and MO3.13 Cell Lines as a Model to Study Oligodendrocyte Functioning.

    abstract::Myelination of neuronal axons is essential for proper brain functioning and requires mature myelinating oligodendrocytes (myOLs). The human OL cell lines HOG and MO3.13 have been widely used as in vitro models to study OL (dys) functioning. Here we applied a number of protocols aimed at differentiating HOG and MO3.13 ...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8091096

    authors: De Kleijn KMA,Zuure WA,Peijnenborg J,Heuvelmans JM,Martens GJM

    更新日期:2019-09-17 00:00:00

  • Circulating Non-Coding RNAs in Head and Neck Cancer: Roles in Diagnosis, Prognosis, and Therapy Monitoring.

    abstract::Head and neck cancer (HNC), the seventh most common form of cancer worldwide, is a group of epithelial malignancies affecting sites in the upper aerodigestive tract. The 5-year overall survival for patients with HNC has stayed around 40-50% for decades, with mortality being attributable mainly to late diagnosis and re...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells10010048

    authors: Diez-Fraile A,Ceulaer J,Derpoorter C,Spaas C,Backer T,Lamoral P,Abeloos J,Lammens T

    更新日期:2020-12-31 00:00:00

  • Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Enhances Activation of STAT3/NLRC4 Inflammasome Signaling Axis through PKCδ in Astrocytes: Implications for Parkinson's Disease.

    abstract::Astrocytic dysfunction has been implicated in Parkinson's disease (PD) pathogenesis. While the Tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 signaling axis is known to play a role in PD-like neuropathology, the molecular mechanisms that govern this process remain poorly understood. Herein, we show ...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9081831

    authors: Samidurai M,Tarale P,Janarthanam C,Estrada CG,Gordon R,Zenitsky G,Jin H,Anantharam V,Kanthasamy AG,Kanthasamy A

    更新日期:2020-08-04 00:00:00

  • PML Bodies in Mitosis.

    abstract::Promyelocytic leukemia (PML) bodies are dynamic intracellular structures that recruit and release a variety of different proteins in response to stress, virus infection, DNA damage and cell cycle progression. While PML bodies primarily are regarded as nuclear compartments, they are forced to travel to the cytoplasm ea...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells8080893

    authors: Lång A,Lång E,Bøe SO

    更新日期:2019-08-14 00:00:00

  • The Essential Role of anxA2 in Langerhans Cell Birbeck Granules Formation.

    abstract::Langerhans cells (LC) are the resident antigen presenting cells of the mucosal epithelium and play an essential role in initiating immune responses. LC are the only cells in the body to contain Birbeck granules (BG), which are unique cytoplasmic organelles comprised of c-type lectin langerin. Studies of BG have histor...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9040974

    authors: Thornton SM,Samararatne VD,Skeate JG,Buser C,Lühen KP,Taylor JR,Da Silva DM,Kast WM

    更新日期:2020-04-15 00:00:00

  • Fluorescent, Bioluminescent, and Optogenetic Approaches to Study Excitable Physiology in the Single Cardiomyocyte.

    abstract::This review briefly summarizes the single cell application of classical chemical dyes used to visualize cardiomyocyte physiology and their undesirable toxicities which have the potential to confound experimental observations. We will discuss, in detail, the more recent iterative development of fluorescent and biolumin...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells7060051

    authors: Broyles CN,Robinson P,Daniels MJ

    更新日期:2018-05-31 00:00:00

  • Amelioration of Congenital Tufting Enteropathy in EpCAM (TROP1)-Deficient Mice via Heterotopic Expression of TROP2 in Intestinal Epithelial Cells.

    abstract::TROP1 (EpCAM) and TROP2 are homologous cell surface proteins that are widely expressed, and often co-expressed, in developing and adult epithelia. Various functions have been ascribed to EpCAM and TROP2, but responsible mechanisms are incompletely characterized and functional equivalence has not been examined. Adult i...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9081847

    authors: Nakato G,Morimura S,Lu M,Feng X,Wu C,Udey MC

    更新日期:2020-08-06 00:00:00

  • Usefulness of the New Hematological Parameter: Reactive Lymphocytes RE-LYMP with Flow Cytometry Markers of Inflammation in COVID-19.

    abstract::Identification of patients with activation of the immune system which indicates the presence of infection is essential, especially in the times of the global coronavirus 2019 (COVID-19) pandemic. The aim of the present study was to evaluate the reactive lymphocytes (RE-LYMP) parameter in COVID-19 and to correlate it w...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells10010082

    authors: Rutkowska E,Kwiecień I,Kulik K,Chełstowska B,Kłos K,Rzepecki P,Chciałowski A

    更新日期:2021-01-06 00:00:00

  • Regulation of Acetylcholine Quantal Release by Coupled Thrombin/BDNF Signaling in Mouse Motor Synapses.

    abstract::The aim of this study was to compare the acute effects of thrombin and brain-derived neurotrophic factor (BDNF) on spontaneous miniature endplate potentials (MEPPs) and multiquantal evoked endplate potentials (EPPs) in mouse neuromuscular junctions (NMJs) of m. diaphragma and m. EDL. Intracellular microelectrode recor...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8070762

    authors: Gaydukov A,Bogacheva P,Tarasova E,Molchanova A,Miteva A,Pravdivceva E,Balezina O

    更新日期:2019-07-22 00:00:00

  • Diverse Roles of Annexin A6 in Triple-Negative Breast Cancer Diagnosis, Prognosis and EGFR-Targeted Therapies.

    abstract::The calcium (Ca2+)-dependent membrane-binding Annexin A6 (AnxA6), is a multifunctional, predominantly intracellular scaffolding protein, now known to play relevant roles in different cancer types through diverse, often cell-type-specific mechanisms. AnxA6 is differentially expressed in various stages/subtypes of sever...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9081855

    authors: Korolkova OY,Widatalla SE,Williams SD,Whalen DS,Beasley HK,Ochieng J,Grewal T,Sakwe AM

    更新日期:2020-08-07 00:00:00

  • Myocardial Adaptation in Pseudohypoxia: Signaling and Regulation of mPTP via Mitochondrial Connexin 43 and Cardiolipin.

    abstract::Therapies intended to mitigate cardiovascular complications cannot be applied in practice without detailed knowledge of molecular mechanisms. Mitochondria, as the end-effector of cardioprotection, represent one of the possible therapeutic approaches. The present review provides an overview of factors affecting the reg...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells8111449

    authors: Ferko M,Andelová N,Szeiffová Bačová B,Jašová M

    更新日期:2019-11-17 00:00:00

  • Competing Endogenous RNAs, Non-Coding RNAs and Diseases: An Intertwined Story.

    abstract::MicroRNAs (miRNAs), a class of small non-coding RNA molecules, are responsible for RNA silencing and post-transcriptional regulation of gene expression. They can mediate a fine-tuned crosstalk among coding and non-coding RNA molecules sharing miRNA response elements (MREs). In a suitable environment, both coding and n...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9071574

    authors: Ala U

    更新日期:2020-06-28 00:00:00

  • Nuclear Envelope Proteins Modulating the Heterochromatin Formation and Functions in Fission Yeast.

    abstract::The nuclear envelope (NE) consists of the inner and outer nuclear membranes (INM and ONM), and the nuclear pore complex (NPC), which penetrates the double membrane. ONM continues with the endoplasmic reticulum (ER). INM and NPC can interact with chromatin to regulate the genetic activities of the chromosome. Studies i...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9081908

    authors: Hirano Y,Asakawa H,Sakuno T,Haraguchi T,Hiraoka Y

    更新日期:2020-08-16 00:00:00

  • Role of Exosomes in the Regulation of T-cell Mediated Immune Responses and in Autoimmune Disease.

    abstract::: T-cell mediated immune responses should be regulated to avoid the development of autoimmune or chronic inflammatory diseases. Several mechanisms have been described to regulate this process, namely death of overactivated T cells by cytokine deprivation, suppression by T regulatory cells (Treg), induction of expressi...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells8020154

    authors: Anel A,Gallego-Lleyda A,de Miguel D,Naval J,Martínez-Lostao L

    更新日期:2019-02-12 00:00:00

  • Use of a Hybrid Adeno-Associated Viral Vector Transposon System to Deliver the Insulin Gene to Diabetic NOD Mice.

    abstract::Previously, we used a lentiviral vector to deliver furin-cleavable human insulin (INS-FUR) to the livers in several animal models of diabetes using intervallic infusion in full flow occlusion (FFO), with resultant reversal of diabetes, restoration of glucose tolerance and pancreatic transdifferentiation (PT), due to t...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9102227

    authors: La QT,Ren B,Logan GJ,Cunningham SC,Khandekar N,Nassif NT,O'Brien BA,Alexander IE,Simpson AM

    更新日期:2020-10-02 00:00:00

  • ER-to-Golgi Transport in HeLa Cells Displays High Resilience to Ca2+ and Energy Stresses.

    abstract::One third of all human proteins are either transmembrane or soluble secretory proteins that first target the endoplasmic reticulum (ER). These proteins subsequently leave the ER and enter the Golgi apparatus via ER-Golgi intermediate vesicular structures. Live-cell imaging of cargos fused to fluorescent proteins (FPs)...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9102311

    authors: Rauter T,Burgstaller S,Gottschalk B,Ramadani-Muja J,Bischof H,Hay JC,Graier WF,Malli R

    更新日期:2020-10-17 00:00:00

  • ZMPSTE24 Is Associated with Elevated Inflammation and Progerin mRNA.

    abstract::Lamins are important filaments forming the inner nuclear membrane. Lamin A is processed by zinc metalloproteinase (ZMPSTE24). Failure to cleave a truncated form of prelamin A-also called progerin-causes Hutchinson-Gilford progeria syndrome a well-known premature aging disease. Minor levels of progerin are readily expr...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9091981

    authors: Messner M,Ghadge SK,Maurer T,Graber M,Staggl S,Christine Maier S,Pölzl G,Zaruba MM

    更新日期:2020-08-28 00:00:00

  • Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives.

    abstract::Evolutionarily conserved Notch plays a critical role in embryonic development and cellular self-renewal. It has both tumour suppressor and oncogenic activity, the latter of which is widely described. Notch-activating mutations are associated with haematological malignancies and several solid tumours including breast, ...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9061503

    authors: Moore G,Annett S,McClements L,Robson T

    更新日期:2020-06-20 00:00:00

  • Upregulation of Mitochondrial Redox Sensitive Proteins in LPS-Treated Stefin B-Deficient Macrophages.

    abstract::Stefin B (cystatin B) is an intracellular inhibitor of cysteine cathepsins and mutations in the stefin B gene, resulting in the development of Unverricht-Lundborg disease, which is a form of myoclonic epilepsy. It was suggested that a key mechanism behind stefin B-mediated disease progression was impaired redox homeos...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8121476

    authors: Trstenjak Prebanda M,Završnik J,Turk B,Kopitar Jerala N

    更新日期:2019-11-21 00:00:00

  • TRPV1 and Endocannabinoids: Emerging Molecular Signals that Modulate Mammalian Vision.

    abstract::Transient Receptor Potential Vanilloid 1 (TRPV1) subunits form a polymodal cation channel responsive to capsaicin, heat, acidity and endogenous metabolites of polyunsaturated fatty acids. While originally reported to serve as a pain and heat detector in the peripheral nervous system, TRPV1 has been implicated in the m...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells3030914

    authors: Ryskamp DA,Redmon S,Jo AO,Križaj D

    更新日期:2014-09-12 00:00:00

  • GSK3β: A Master Player in Depressive Disorder Pathogenesis and Treatment Responsiveness.

    abstract::Glycogen synthase kinase 3β (GSK3β), originally described as a negative regulator of glycogen synthesis, is a molecular hub linking numerous signaling pathways in a cell. Specific GSK3β inhibitors have anti-depressant effects and reduce depressive-like behavior in animal models of depression. Therefore, GSK3β is sugge...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9030727

    authors: Duda P,Hajka D,Wójcicka O,Rakus D,Gizak A

    更新日期:2020-03-16 00:00:00

  • Emerging Noninvasive Biomarkers, and Medical Management Strategies for Alcoholic Hepatitis: Present Understanding and Scope.

    abstract::Alcohol use disorder is associated with a wide array of hepatic pathologies ranging from steatosis to alcoholic-related cirrhosis (AC), alcoholic hepatitis (AH), or hepatocellular carcinoma (HCC). Biomarkers are categorized into two main categories: biomarkers associated with alcohol consumption and biomarkers of alco...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9030524

    authors: Gala KS,Vatsalya V

    更新日期:2020-02-25 00:00:00

  • The Role of Gut-Derived Microbial Antigens on Liver Fibrosis Initiation and Progression.

    abstract::Intestinal dysbiosis has recently become known as an important driver of gastrointestinal and liver disease. It remains poorly understood, however, how gastrointestinal microbes bypass the intestinal mucosa and enter systemic circulation to enact an inflammatory immune response. In the context of chronic liver disease...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells8111324

    authors: Chen D,Le TH,Shahidipour H,Read SA,Ahlenstiel G

    更新日期:2019-10-27 00:00:00

  • p53 -Dependent and -Independent Nucleolar Stress Responses.

    abstract::The nucleolus has emerged as a cellular stress sensor and key regulator of p53-dependent and -independent stress responses. A variety of abnormal metabolic conditions, cytotoxic compounds, and physical insults induce alterations in nucleolar structure and function, a situation known as nucleolar or ribosomal stress. R...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells1040774

    authors: Holmberg Olausson K,Nistér M,Lindström MS

    更新日期:2012-10-15 00:00:00

  • Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for Cell Cycle Arrest, Apoptosis and Autophagy.

    abstract::Recent studies have proven that Dimethylfumarate (DMF) has a marked anti-proliferative impact on diverse cancer entities e.g., on malignant melanoma. To explore its anti-tumorigenic potential, we examined the effects of DMF on human colon carcinoma cell lines and the underlying mechanisms of action. Human colon cancer...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8111329

    authors: Kaluzki I,Hailemariam-Jahn T,Doll M,Kaufmann R,Balermpas P,Zöller N,Kippenberger S,Meissner M

    更新日期:2019-10-28 00:00:00

  • Extrachromosomal Histone H2B Contributes to the Formation of the Abscission Site for Cell Division.

    abstract::Histones are constitutive components of nucleosomes and key regulators of chromatin structure. We previously observed that an extrachromosomal histone H2B (ecH2B) localizes at the intercellular bridge (ICB) connecting the two daughter cells during cytokinesis independently of DNA and RNA. Here, we show that ecH2B bind...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8111391

    authors: Monteonofrio L,Valente D,Rinaldo C,Soddu S

    更新日期:2019-11-05 00:00:00

  • Epigenetically Altered T Cells Contribute to Lupus Flares.

    abstract::Lupus flares when genetically predisposed people encounter exogenous agents such as infections and sun exposure and drugs such as procainamide and hydralazine, but the mechanisms by which these agents trigger the flares has been unclear. Current evidence indicates that procainamide and hydralazine, as well as inflamma...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells8020127

    authors: Richardson B

    更新日期:2019-02-05 00:00:00

  • Influence of ARHGAP29 on the Invasion of Mesenchymal-Transformed Breast Cancer Cells.

    abstract::Aggressive and mesenchymal-transformed breast cancer cells show high expression levels of Rho GTPase activating protein 29 (ARHGAP29), a negative regulator of RhoA. ARHGAP29 was the only one of 32 GTPase-activating enzymes whose expression significantly increased after the induction of mesenchymal transformation in br...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9122616

    authors: Kolb K,Hellinger J,Kansy M,Wegwitz F,Bauerschmitz G,Emons G,Gründker C

    更新日期:2020-12-05 00:00:00