scholarly journals G-quadruplex inducer/stabilizer pyridostatin targets SUB1 to promote cytotoxicity of a transplatinum complex

2021 ◽  
Author(s):  
Yinzhu Hou ◽  
Tieliang Gan ◽  
Tiantian Fang ◽  
Yao Zhao ◽  
Qun Luo ◽  
...  
Keyword(s):  
Cell Cycle Regulation ◽  
Rational Design ◽  
Target Genes ◽  
Anticancer Agent ◽  
Bioinformatics Analysis ◽  
Biological Functions ◽  
Dna Lesion ◽  
Platinum Anticancer Drugs ◽  
G Quadruplex ◽  
Cycle Regulation

Pyridostatin (PDS) is a well-known G-quadruplex (G4) inducer and stabilizer, yet its target genes have remained unclear. Herein, combining mass spectrometry based proteomics strategy with bioinformatics analysis, we revealed that PDS significantly downregulated 22 proteins, of which the genes contain rich G4 potential sequences, in HeLa cancer cells, consequently upregulating 16 proteins remarkably. The PDS-regulated proteins appeared to work synergistically to activate cyclin and cell cycle regulation, and to restrain the inhibition of ARE-mediated mRNA decay pathway, suggesting that PDS itself is not a potential anticancer agent, at least towards HeLa cancer. Importantly, among the PDS targeted genes, SUB1, which expresses the human positive cofactor and DNA lesion sensor PC4, was down-regulated by 4.76-fold. Further studies demonstrated that the downregulation of PC4 dramatically promoted the cytotoxicity of trans-[PtCl2(NH3)(thiazole)] towards HeLa cells to a similar level to that of cisplatin, contributable to retarding the repair of 1,3-trans-platinated DNA lesion mediated by PC4. These findings not only provide new insights into better understanding on the biological functions of PDS, but also implicate a strategy for the rational design of novel multi-targeting platinum anticancer drugs via conjugation of PDS as a ligand to the coordination scaffold of transplatin for battling drug resistance to cisplatin.

scholarly journals Computational Study of Lactucine and its Derivatives with Apoptosis Inducing Proteins of Various Pathways

2021 ◽  
Author(s):  
Mamta Arya ◽  
Apoorv Tiwari ◽  
Dev Bukhsh Singh ◽  
Gohar Taj
Keyword(s):  
Cell Cycle ◽  
Clinical Trials ◽  
Hydrogen Bonding ◽  
Cell Cycle Regulation ◽  
Anticancer Agent ◽  
Computational Study ◽  
Human Leukemia ◽  
Chemotherapeutic Drugs ◽  
Cycle Regulation

Abstract In the present computational study, we found that lactucin 15-oxalate a chemical component present in the cichorium intybus (chicory) has a potential apoptosis inducing effect in human leukemia cancer cell and may acts as an anticancer agent. Lactucine and its derivatives were used as ligand molecules to trace out its binding interactions with proteins involved in apoptosis and these ligands were docked with different apoptosis inducing protein such as caspases, cytochrome C, apaf-1, CDKs, etc involved in cell cycle regulation. Among lactucine derivatives, the lactucin 15-oxalate showed virtuous affinity for the apoptosis inducing protein. In addition to this, the number of the hydrogen bonding was higher with lactucin 15-oxalate as compare to other derivatives which indicates its suitability as an anticancer agent. An apoptosis inducing agent if implemented for the treatment of leukemia cancer, then it can reduce the use of multidrug dose therapy and chemotherapeutic drugs. However, different in vitro as well as clinical trials are needed for further validation of the lactucin 15-oxalate.

scholarly journals Translational repression of cyclin D3 by a stable G-quadruplex in its 5′ UTR: implications for cell cycle regulation

RNA Biology ◽  
2012 ◽  
Vol 9 (8) ◽  
pp. 1099-1109 ◽  
Author(s):  
Heng-You Weng ◽  
Hui-Lin Huang ◽  
Pan-Pan Zhao ◽  
Hui Zhou ◽  
Liang-Hu Qu
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Cyclin D3 ◽  
Translational Repression ◽  
G Quadruplex ◽  
Cycle Regulation

scholarly journals PITHD1 is a proteasome-interacting protein essential for male fertilization

2020 ◽  
Vol 295 (6) ◽  
pp. 1658-1672 ◽  
Author(s):  
Hiroyuki Kondo ◽  
Takafumi Matsumura ◽  
Mari Kaneko ◽  
Kenichi Inoue ◽  
Hidetaka Kosako ◽  
...  
Keyword(s):  
Cell Cycle Regulation ◽  
T Cell Development ◽  
Proteasome Activity ◽  
Protein Homeostasis ◽  
Biological Functions ◽  
Interacting Protein ◽  
Thymic Epithelium ◽  
Cycle Regulation ◽  
Deficient Mice

The proteasome is a protein-degrading molecular complex that is necessary for protein homeostasis and various biological functions, including cell cycle regulation, signal transduction, and immune response. Proteasome activity is finely regulated by a variety of proteasome-interacting molecules. PITHD1 is a recently described molecule that has a domain putatively capable of interacting with the proteasome. However, it is unknown whether PITHD1 can actually bind to proteasomes and what it does in vivo. Here we report that PITHD1 is detected specifically in the spermatids in the testis and the cortical thymic epithelium in the thymus. Interestingly, PITHD1 associates with immunoproteasomes in the testis, but not with thymoproteasomes in the thymus. Mice deficient in PITHD1 exhibit severe male infertility accompanied with morphological abnormalities and impaired motility of spermatozoa. Furthermore, PITHD1 deficiency reduces proteasome activity in the testis and alters the amount of proteins that are important for fertilization capability by the sperm. However, the PITHD1-deficient mice demonstrate no detectable defects in the thymus, including T cell development. Collectively, our results identify PITHD1 as a proteasome-interacting protein that plays a nonredundant role in the male reproductive system.

scholarly journals Peptidyl-Prolyl cis/trans Isomerase-Independent Functional NifH Mutant of Azotobacter vinelandii

2006 ◽  
Vol 188 (16) ◽  
pp. 6020-6025 ◽  
Author(s):  
Nara Gavini ◽  
Sudheer Tungtur ◽  
Lakshmi Pulakat
Keyword(s):  
Cell Cycle ◽  
Bacterial Infection ◽  
Cell Cycle Regulation ◽  
Azotobacter Vinelandii ◽  
The Other ◽  
Molecular Signature ◽  
Accessory Protein ◽  
Biological Functions ◽  
Eukaryotic Proteins ◽  
Cycle Regulation

ABSTRACT Peptidyl-prolyl cis/trans isomerases (PPIases) play a pivotal role in catalyzing the correct folding of many prokaryotic and eukaryotic proteins that are implicated in a variety of biological functions, ranging from cell cycle regulation to bacterial infection. The nif accessory protein NifM, which is essential for the biogenesis of a functional NifH component of nitrogenase, is a PPIase. To understand the nature of the molecular signature that defines the NifM dependence of NifH, we screened a library of nifH mutants in the nitrogen-fixing bacterium Azotobacter vinelandii for mutants that acquired NifM independence. Here, we report that NifH can acquire NifM independence when the conserved Pro258 located in the C-terminal region of NifH, which wraps around the other subunit in the NifH dimer, is replaced by serine.

scholarly journals Potent Antifungal Properties of Dimeric Acylphloroglucinols from Hypericum mexicanum and Mechanism of Action of a Highly Active 3′Prenyl Uliginosin B

Metabolites ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 459
Author(s):  
Noemi Tocci ◽  
Tobias Weil ◽  
Daniele Perenzoni ◽  
Marco Moretto ◽  
Nicolai Nürk ◽  
...  
Keyword(s):  
Cell Cycle Regulation ◽  
Target Genes ◽  
Fungal Growth ◽  
Great Promise ◽  
Liquid Chromatography Mass Spectrometry ◽  
Highly Active ◽  
Fluconazole Resistant ◽  
Resistant Strains ◽  
Fungal Growth Inhibition ◽  
Cycle Regulation

The success of antifungal therapies is often hindered by the limited number of available drugs. To close the gap in the antifungal pipeline, the search of novel leads is of primary importance, and here the exploration of neglected plants has great promise for the discovery of new principles. Through bioassay-guided isolation, uliginosin B and five new dimeric acylphloroglucinols (uliginosins C-D, and 3′prenyl uliginosins B-D), besides cembrenoids, have been isolated from the lipophilic extract of Hypericum mexicanum. Their structures were elucidated by a combination of Liquid Chromatography - Mass Spectrometry LC-MS and Nuclear Magnetic Resonance (NMR) measurements. The compounds showed strong anti-Candida activity, also against fluconazole-resistant strains, with fungal growth inhibition properties at concentrations ranging from 3 to 32 µM, and reduced or absent cytotoxicity against human cell lines. A chemogenomic screen of 3′prenyl uliginosin B revealed target genes that are important for cell cycle regulation and cytoskeleton assembly in fungi. Taken together, our study suggests dimeric acylphloroglucinols as potential candidates for the development of alternative antifungal therapies.

Abstract 1813: FOXM1 target genes associated with cell cycle regulation predict breast cancer metastatic outcome.

2013 ◽  
Author(s):  
Christina Yau ◽  
Laurence Meyer ◽  
Stephen Benz ◽  
Charles Vaske ◽  
Gary Scott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Target Genes ◽  
Cycle Regulation
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