scholarly journals Autophagy and Tumor Database: ATdb, a novel database connecting autophagy and tumor

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Kelie Chen ◽  
Dexin Yang ◽  
Fan Zhao ◽  
Shengchao Wang ◽  
Yao Ye ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Post Translational Modifications ◽  
Tumor Subtypes ◽  
Autophagy Gene ◽  
Anti Cancer ◽  
Functional Implications ◽  
Tumor Research ◽  
Non Coding Rnas ◽  
Context Dependent

Abstract Autophagy is an essential cellular process that is closely implicated in diverse pathophysiological processes and a variety of human diseases, especially tumors. Autophagy is regarded as not only an anti-cancer process in tumorigenesis but also a pro-tumor process in progression and metastasis according to current research. It means the role of autophagy in tumor is considered to be complex, controversial and context dependent. Hence, a comprehensive database is of great significance to obtain an in-depth understanding of such complex correlations between autophagy and tumor. To achieve this objective, here we developed the Autophagy and Tumor Database (named as ATdb, http://www.bigzju.com/ATdb/#/) to compile the published information concerning autophagy and tumor research. ATdb connected 25 types of tumors with 137 genes required for autophagy-related pathways, containing 219 population filters, 2650 hazard ratio trend plots, 658 interacting microRNAs, 266 interacting long non-coding RNAs, 155 post-translational modifications, 298 DNA methylation records, 331 animal models and 70 clinical trials. ATdb could enable users to search, browse, download and carry out efficient online analysis. For instance, users can make prediction of autophagy gene regulators in a context-dependent manner and in a precise subpopulation and tumor subtypes. Also, it is feasible in ATdb to cluster tumors into distinguished groups based on the gene-related long non-coding RNAs to gain novel insights into their potential functional implications. Thus, ATdb offers a powerful online database for the autophagy community to explore the complex world of autophagy and tumor. Database URL: http://www.bigzju.com/ATdb/#/

scholarly journals Generation of a Quantitative Luciferase Reporter for Sox9 SUMOylation

2020 ◽  
Vol 21 (4) ◽  
pp. 1274
Author(s):  
Hideka Saotome ◽  
Atsumi Ito ◽  
Atsushi Kubo ◽  
Masafumi Inui
Keyword(s):  
Cell Types ◽  
Live Cells ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Post Translational Modifications ◽  
Extracellular Signal ◽  
Multiple Cell ◽  
Sox9 Activity ◽  
Reporter Signal

Sox9 is a master transcription factor for chondrogenesis, which is essential for chondrocyte proliferation, differentiation, and maintenance. Sox9 activity is regulated by multiple layers, including post-translational modifications, such as SUMOylation. A detection method for visualizing the SUMOylation in live cells is required to fully understand the role of Sox9 SUMOylation. In this study, we generated a quantitative reporter for Sox9 SUMOylation that is based on the NanoBiT system. The simultaneous expression of Sox9 and SUMO1 constructs that are conjugated with NanoBiT fragments in HEK293T cells induced luciferase activity in SUMOylation target residue of Sox9-dependent manner. Furthermore, the reporter signal could be detected from both cell lysates and live cells. The signal level of our reporter responded to the co-expression of SUMOylation or deSUMOylation enzymes by several fold, showing dynamic potency of the reporter. The reporter was active in multiple cell types, including ATDC5 cells, which have chondrogenic potential. Finally, using this reporter, we revealed a extracellular signal conditions that can increase the amount of SUMOylated Sox9. In summary, we generated a novel reporter that was capable of quantitatively visualizing the Sox9-SUMOylation level in live cells. This reporter will be useful for understanding the dynamism of Sox9 regulation during chondrogenesis.

scholarly journals Non-Coding RNAs in Cartilage Development: An Updated Review

2019 ◽  
Vol 20 (18) ◽  
pp. 4475 ◽  
Author(s):  
Ehsan Razmara ◽  
Amirreza Bitaraf ◽  
Hassan Yousefi ◽  
Tina H. Nguyen ◽  
Masoud Garshasbi ◽  
...  
Keyword(s):  
Cell Biology ◽  
Endochondral Ossification ◽  
Association Studies ◽  
Post Translational Modifications ◽  
Cartilage Development ◽  
Complex Process ◽  
Cartilage Cells ◽  
Non Coding Rnas ◽  
Skeletal Disorders

In the development of the skeleton, the long bones are arising from the process of endochondral ossification (EO) in which cartilage is replaced by bone. This complex process is regulated by various factors including genetic, epigenetic, and environmental elements. It is recognized that DNA methylation, higher-order chromatin structure, and post-translational modifications of histones regulate the EO. With emerging understanding, non-coding RNAs (ncRNAs) have been identified as another mode of EO regulation, which is consist of microRNAs (miRNAs or miRs) and long non-coding RNAs (lncRNAs). There is expanding experimental evidence to unlock the role of ncRNAs in the differentiation of cartilage cells, as well as the pathogenesis of several skeletal disorders including osteoarthritis. Cutting-edge technologies such as epigenome-wide association studies have been employed to reveal disease-specific patterns regarding ncRNAs. This opens a new avenue of our understanding of skeletal cell biology, and may also identify potential epigenetic-based biomarkers. In this review, we provide an updated overview of recent advances in the role of ncRNAs especially focus on miRNA and lncRNA in the development of bone from cartilage, as well as their roles in skeletal pathophysiology.

scholarly journals USP52 regulates DNA end resection and chemosensitivity through removing inhibitory ubiquitination from CtIP

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ming Gao ◽  
Guijie Guo ◽  
Jinzhou Huang ◽  
Jake A. Kloeber ◽  
Fei Zhao ◽  
...  
Keyword(s):  
Parp Inhibition ◽  
Dependent Manner ◽  
Interacting Protein ◽  
Post Translational Modifications ◽  
Regulatory Complexity ◽  
Dna End Resection ◽  
End Resection

Abstract Human C-terminal binding protein (CtBP)–interacting protein (CtIP) is a central regulator to initiate DNA end resection and homologous recombination (HR). Several studies have shown that post-translational modifications control the activity or expression of CtIP. However, it remains unclear whether and how cells restrain CtIP activity in unstressed cells and activate CtIP when needed. Here, we identify that USP52 directly interacts with and deubiquitinates CtIP, thereby promoting DNA end resection and HR. Mechanistically, USP52 removes the ubiquitination of CtIP to facilitate the phosphorylation and activation of CtIP at Thr-847. In addition, USP52 is phosphorylated by ATM at Ser-1003 after DNA damage, which enhances the catalytic activity of USP52. Furthermore, depletion of USP52 sensitizes cells to PARP inhibition in a CtIP-dependent manner in vitro and in vivo. Collectively, our findings reveal the key role of USP52 and the regulatory complexity of CtIP deubiquitination in DNA repair.

Involvement of inositol 1,4,5-trisphosphate-mediated Ca2+ release in early and late events of mouse egg activation

Development ◽  
1994 ◽  
Vol 120 (7) ◽  
pp. 1851-1859 ◽  
Author(s):  
Z. Xu ◽  
G.S. Kopf ◽  
R.M. Schultz
Keyword(s):  
Inhibitory Effect ◽  
Egg Activation ◽  
Dependent Manner ◽  
Ip3 Receptor ◽  
Concentration Dependent Manner ◽  
Post Translational Modifications ◽  
Inositol 1,4,5 Trisphosphate ◽  
Mammalian Eggs ◽  
Mouse Egg

Sperm-induced activation of mammalian eggs is associated with a transient increase in the concentration of intracellular Ca2+. The role of inositol 1,4,5-trisphosphate (IP3)-mediated release of Ca2+ from intracellular stores during mouse egg activation was examined in the present study by determining the effects of microinjected monoclonal antibody (mAb) 18A10, which binds to the IP3 receptor and inhibits IP3-induced Ca2+ release, on endpoints of egg activation following insemination. The antibody inhibited in a concentration-dependent manner the ZP2 to ZP2f conversion that is involved in the zona pellucida block to polyspermy, as well as the ZP2 to ZP2f conversion promoted by microinjected IP3 in non-inseminated eggs. As anticipated, inseminated eggs that had been microinjected with the antibody were polyspermic. In addition, the antibody inhibited the fertilization-associated decrease in H1 kinase activity and pronucleus formation, and the concentration dependence for inhibition of these events was similar to that observed for inhibiting the ZP2 to ZP2f conversion. Last, the antibody inhibited the fertilization-induced recruitment of maternal mRNAs and post-translational modifications of proteins. In each case, eggs microinjected with the mAb 4C11, which also binds to the IP3 receptor but does not inhibit IP3-induced Ca2+ release, had no inhibitory effect on fertilization and egg activation. Results of these studies suggest that IP3-mediated Ca2+ release is essential for both early and late events of mouse egg activation.

scholarly journals Regulation of Hippo, TGFβ/SMAD, Wnt/β-Catenin, JAK/STAT, and NOTCH by Long Non-Coding RNAs in Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Ammad Ahmad Farooqi ◽  
Sawera Nayyab ◽  
Chiara Martinelli ◽  
Rossana Berardi ◽  
Hector Katifelis ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genetic Material ◽  
Post Translational Modifications ◽  
Non Coding Rna ◽  
Competitive Endogenous Rnas ◽  
Non Coding Rnas ◽  
Underlying Mechanisms ◽  
Molecular Pathophysiology ◽  
Modern Era

Rapidly evolving and ever-increasing knowledge of the molecular pathophysiology of pancreatic cancer has leveraged our understanding altogether to a next level. Compared to the exciting ground-breaking discoveries related to underlying mechanisms of pancreatic cancer onset and progression, however, there had been relatively few advances in the therapeutic options available for the treatment. Since the discovery of the DNA structure as a helix which replicates semi-conservatively to pass the genetic material to the progeny, there has been conceptual refinement and continuous addition of missing pieces to complete the landscape of central dogma. Starting from transcription to translation, modern era has witnessed non-coding RNA discovery and central role of these versatile regulators in onset and progression of pancreatic cancer. Long non-coding RNAs (lncRNAs) have been shown to act as competitive endogenous RNAs through sequestration and competitive binding to myriad of microRNAs in different cancers. In this article, we set spotlight on emerging evidence of regulation of different signaling pathways (Hippo, TGFβ/SMAD, Wnt/β-Catenin, JAK/STAT and NOTCH) by lncRNAs. Conceptual refinements have enabled us to understand how lncRNAs play central role in post-translational modifications of various proteins and how lncRNAs work with epigenetic-associated machinery to transcriptionally regulate gene network in pancreatic cancer.

scholarly journals The Tubulin Code in Mitosis and Cancer

2020 ◽  
Author(s):  
Danilo Lopes ◽  
Helder Maiato
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Chromosomal Instability ◽  
Metaphase Plate ◽  
Post Translational Modifications ◽  
Alpha Tubulin ◽  
Therapeutic Implications ◽  
Human Cancers ◽  
Functional Implications

The “tubulin code” combines different α/β-tubulin isotypes with several post-translational modifications (PTMs) to generate microtubule diversity in cells. During cell division, specific microtubule populations in the mitotic spindle are differentially modified, but only recently has the functional significance of these modifications started to be elucidated. In particular, α-tubulin detyrosination of stable microtubules in the spindle was shown to guide chromosomes during congression to the metaphase plate and allow the discrimination of mitotic errors, whose correction is required to prevent chromosomal instability (CIN), a hallmark of human cancers. Although alterations in certain tubulin PTMs have been reported in human cancers, it remains unclear whether and how tubulin PTMs have any functional implications for cancer cell properties. Here we review the role of the tubulin code in chromosome segregation during mitosis, together with the emerging cancer tubulin code and discuss possible links, as well as the respective diagnostic, prognostic and therapeutic implications for human cancers.

scholarly journals Apoptosis is triggered by melatonin in an in vivo model of ovarian carcinoma

2015 ◽  
Vol 23 (2) ◽  
pp. 65-76 ◽  
Author(s):  
Luiz Gustavo A Chuffa ◽  
Michelly S Alves ◽  
Marcelo Martinez ◽  
Isabel Cristina C Camargo ◽  
Patricia F F Pinheiro ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Body Weight Gain ◽  
In Vivo Model ◽  
Multiple Tumor ◽  
Tumor Subtypes ◽  
Sham Surgery ◽  
Therapeutic Value ◽  
Anti Cancer

Apoptosis plays an important role in the treatment of cancer, and targeting apoptosis-related molecules in ovarian cancer (OC) is of great therapeutic value. Melatonin (Mel) is an indoleamine displaying several anti-cancer properties and has been reported to modulate apoptosis signaling in multiple tumor subtypes. We investigated OC and the role of Mel therapy on the pro-apoptotic (p53, BAX, caspase-3, and cleaved caspase-3) and anti-apoptotic (Bcl-2 and survivin) proteins in an ethanol (EtOH)-preferring rat model. To induce OC, the left ovary was injected directly with a single dose of 100 μg 7,12-dimethylbenz(a)anthracene dissolved in 10 μl of sesame oil under the bursa. Right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of Mel (200 μg/100 g BW per day) for 60 days. Body weight gain, EtOH consumption, and energy intake were unaffected by the treatments. Interestingly, absolute and relative OC masses showed a significant reduction after Mel therapy, regardless of EtOH consumption. To accomplish OC-related apoptosis, we first observed that p53, BAX, caspase-3, and cleaved caspase-3 were downregulated in OC tissue while Bcl-2 and survivin were overexpressed. Notably, Mel therapy and EtOH intake promoted apoptosis along with the upregulation of p53, BAX, and cleaved caspase-3. Fragmentation of DNA observed by TUNEL-positive nuclei was also enhanced following Mel treatment. In addition, Bcl-2 was downregulated by the EtOH intake and lower survivin levels were observed after Mel therapy. Taken together, these results suggest that Mel induce apoptosis in OC cells of EtOH-preferring animals.

Abstract P210: (Pro)Renin Receptor Regulates Potassium Homeostasis via Intrarenal Aldosterone

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Chuanming Xu ◽  
Aihua Lu ◽  
Hong Wang ◽  
Hui Fang ◽  
Li Zhou ◽  
...  
Keyword(s):  
Protein Expression ◽  
Potential Role ◽  
Fold Increase ◽  
Dependent Manner ◽  
Sd Rats ◽  
High K ◽  
Functional Implications ◽  
Calcium Activated Potassium Channel ◽  
Dose Dependent

It has been shown that transgenic overexpression of human (pro)renin receptor (PRR) results in elevated aldosterone (Aldo) level with unclear functional implications. The present study examined a potential role of renal PRR during high K + (HK) loading. In normal SD rats, a 1-week HK intake (5% KCl in diet) induced a 3.4-fold increase in renal protein expression of full-length PRR and 4.2-fold increase in urinary excretion of soluble PRR (sPRR). Administration of PRO20, a decoy peptide antagonist of PRR, at 700 μg/kg/d via i.p. injections, to K + -loaded animals elevated plasma K + level (5.72+0.08 vs. 4.84±0.18 mM, p<0.05) and decreased urinary K + excretion (2.52+0.11 vs. 3.43+0.19 mmol/24h, p<0.05), accompanied with a 26.2% reduction of urinary aldosterone (Aldo) excretion. HK downregulated NCC protein expression (57.8%) and upregulated renal protein expression of aldosterone synthase CYP11B2 (229%), ROMK (156%), calcium-activated potassium channel subunit alpha-1 (α-BK) (367%), α-Na + -K + -ATPase (596%), and β-ENaC (155%), all of which were significantly blunted by PRO20 (by 50 - 70%). The same maneuvers were applied to adrenalectomized (ADX) rats. Although plasma Aldo was extremely low and also unresponsive to HK loading, urinary Aldo excretion was elevated by 274% with this treatment, which was abolished by PRO20. The HK-induced responses of the above K + and Na + transporting proteins in ADX rats all persisted and also remained sensitive to PRO20. Additionally, spironolactone treatment in ADX rats was still effective in inhibiting kaliuresis induced by HK loading, resulting in hyperkalemia (Plasma K+: 5.13±0.07 vs. 4.19±0.27 mM, p<0.05). In primary rat IMCD cells, exposure to 10 mM KCl for 24 h augmented PRR protein expression and sPRR release in a time- and dose-dependent manner. HK upregulated Aldo release in parallel with increased CYP11B2 protein expression, which were both attenuated by PRO20 or PRR siRNA. A recombinant sPRR, sPRR-His, stimulated Aldo release and CYP11B2 expression. Taken together, we conclude that HK increased renal PRR expression that stimulates renal synthesis of Aldo that coordinates the response of renal membrane Na + and K + transporting proteins to facilitate K + secretion.

scholarly journals The Tubulin Code in Mitosis and Cancer

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2356
Author(s):  
Danilo Lopes ◽  
Helder Maiato
Keyword(s):  
Cancer Cell ◽  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Metaphase Plate ◽  
Tumor Evolution ◽  
Post Translational Modifications ◽  
Tubulin Isotypes ◽  
Human Cancers ◽  
Functional Implications

The “tubulin code” combines different α/β-tubulin isotypes with several post-translational modifications (PTMs) to generate microtubule diversity in cells. During cell division, specific microtubule populations in the mitotic spindle are differentially modified, but only recently, the functional significance of the tubulin code, with particular emphasis on the role specified by tubulin PTMs, started to be elucidated. This is the case of α-tubulin detyrosination, which was shown to guide chromosomes during congression to the metaphase plate and allow the discrimination of mitotic errors, whose correction is required to prevent chromosomal instability—a hallmark of human cancers implicated in tumor evolution and metastasis. Although alterations in the expression of certain tubulin isotypes and associated PTMs have been reported in human cancers, it remains unclear whether and how the tubulin code has any functional implications for cancer cell properties. Here, we review the role of the tubulin code in chromosome segregation during mitosis and how it impacts cancer cell properties. In this context, we discuss the existence of an emerging “cancer tubulin code” and the respective implications for diagnostic, prognostic and therapeutic purposes.

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