AI Article Synopsis
- HIV-1 Vif targets and degrades cellular proteins, specifically the APOBEC3 antiviral enzymes and regulators of the phosphatase PP2A, to aid its viral survival and propagation.
- Through deep mutagenesis, researchers identified the specific components of Vif necessary for degrading PPP2R5, revealing separation-of-function mutants that affect either PPP2R5 or APOBEC3G degradation.
- The study shows that Vif induces G2 cell cycle arrest via the degradation of PPP2R5, which is crucial for HIV-1's ability to thrive across different strains worldwide.
Article Abstract
HIV-1 Vif hijacks a cellular ubiquitin ligase complex to degrade antiviral APOBEC3 enzymes and PP2A phosphatase regulators (PPP2R5A-E). APOBEC3 counteraction is essential for viral pathogenesis. However, Vif also functions through an unknown mechanism to induce G2 cell cycle arrest. Here, deep mutagenesis is used to define the Vif surface required for PPP2R5 degradation and isolate a panel of separation-of-function mutants (PPP2R5 degradation-deficient and APOBEC3G degradation-proficient). Functional studies with Vif and PPP2R5 mutants were combined to demonstrate that PPP2R5 is, in fact, the target Vif degrades to induce G2 arrest. Pharmacologic and genetic approaches show that direct modulation of PP2A function or depletion of specific PPP2R5 proteins causes an indistinguishable arrest phenotype. Vif function in the cell cycle checkpoint is present in common HIV-1 subtypes worldwide and likely advantageous for viral pathogenesis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903395 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2019.09.057 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In-silico and In-vitro Evaluation of Novel Carboxamide Analogue on the Metastasis of Triple Negative Breast Cancer Cells Utilizing Novel PCPTC-loaded PEGylated-PLGA Nanocarriers.
Appl Biochem Biotechnol
December 2024
Department of Life Science, Sharda School of Basic Sciences and Research, Sharda University, Greater Noida, U.P, 201310, India.
This study aimed to determine the effects of novel N-{3-[(pyridin-4-yl)carbamoyl] phenyl} thiophene-2-carboxamide or PCPTC chemical moiety loaded Poly(lactic-co-glycolic acid)-Poly (Ethylene glycol) or (PLGA-PEGylated) NP as an anti-metastatic Ran GTPase therapeutic agent on MDA-MB231 triple-negative human breast cancer cells. Molecular docking and MD simulation was done to determine the binding potential of novel carboxamide PCPTC with Ran GTPase. PLGA and PLGA-PEG based NP encapsulating PCPTC were fabricated using the Modified Double Emulsion Solvent Evaporation Technique and characterized for size, zeta potential, polydispersity and morphology.
View Article and Find Full Text PDFRole of arbutin in the inhibition of FBXO5 in hepatocellular carcinoma.
Discov Oncol
December 2024
Department of Hygiene, School of Public Health, Bengbu Medical University, Bengbu, 233030, Anhui, People's Republic of China.
Purpose: This work investigated the effect of FBXO5 in hepatocellular carcinoma (HCC) and the mechanism of action of arbutin in its inhibition.
Methods: FBXO5 mRNA and protein expressions in the tumor were assessed using TCGA, ICGC and HPA databases. Cox regression analysis and Kaplan-Meier survival curves were employed to assess the impact of FBXO5 on the survival outcomes of patients with HCC.
Rapamycin and Niacin combination induces apoptosis and cell cycle arrest through autophagy activation on acute myeloid leukemia cells.
Mol Biol Rep
December 2024
Faculty of Life and Natural Sciences, Department of Bioengineering, Abdullah Gül University, Sumer Campus, Kayseri, 38080, Turkey.
Background: Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy caused by disorders in stem cell differentiation and excessive proliferation resulting in clonal expansion of dysfunctional cells called myeloid blasts. The combination of chemotherapeutic agents with natural product-based molecules is promising in the treatment of AML. In this study, we aim to investigate the anti-cancer effect of Rapamycin and Niacin combination on THP-1 and NB4 AML cell lines.
View Article and Find Full Text PDFGenome-Wide Network Analysis of DRG-Sciatic Nerve Network-Inferred Cellular Senescence and Senescence Phenotype in Peripheral Sensory Neurons.
Mol Neurobiol
December 2024
Department of Physical Therapy, School of Health and Social Services, Saitama Prefectural University, 820 San-Nomiya, Koshigaya-Shi, Saitama, 343-8540, Japan.
Accumulation of senescent neurons in the dorsal root ganglion (DRG) is an important tissue phenotype that causes age-related degeneration of peripheral sensory nerves. Senescent neurons are neurons with arrested cell cycle that have undergone cellular senescence but remain in the tissue and play various biological roles. To understand the accumulation of senescent neurons in the DRG during aging, we aimed to elucidate the mechanism that induces cellular senescence in DRG neurons and the role of senescent DRG neurons.
View Article and Find Full Text PDFMicrobe-derived Bisindole Alkaloids with Anticancer Potential and Their Mechanisms: A Comprehensive Review.
Chem Biodivers
December 2024
Shanghai University of Traditional Chinese Medicine, School of Traditional Chinese Medicine, #1200 Cailun road, Shanghai, CHINA.
Bisindole alkaloids constitute a significant class of natural compounds distinguished by their characteristic bisindole structure and renowned for their anticancer properties. Over the past six decades, researchers have isolated 425 microorganism-derived bisindole alkaloids (MDBAs). Among them, 187 MDBAs have demonstrated anticancer properties against various in vitro cancer cell lines, primarily by impeding the cell cycle, restraining cell proliferation, and inducing apoptosis and autophagy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!