Cancer cells are addicted to numerous non-oncogenic traits that enable them to thrive. Proteotoxic stress is one such non-oncogenic trait that is experienced by all tumor cells owing to increased genomic abnormalities and the resulting synthesis and accumulation of non-stoichiometric amounts of cellular proteins. This imbalance in the amounts of proteins ultimately culminates in proteotoxic stress. p97, or valosin-containing protein (VCP), is an ATPase whose function is essential to restore protein homeostasis in the cells. Working in concert with the ubiquitin proteasome system, p97 promotes the retrotranslocation from cellular organelles and/or degradation of misfolded proteins. Consequently, p97 inhibition has emerged as a novel therapeutic target in cancer cells, especially those that have a highly secretory phenotype. This review summarizes our current understanding of the function of p97 in maintaining protein homeostasis and its inhibition with small molecule inhibitors as an emerging strategy to target cancer cells.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971439 | PMC |
| http://dx.doi.org/10.3389/fonc.2016.00181 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Extensive homologous recombination safeguards oocyte genome integrity in mammals.
Nucleic Acids Res
January 2025
MOE Key Laboratory of Biosystems Homeostasis and Protection, College of Life Sciences, Zhejiang University, No.866 Yuhangtang Road, 310058, Hangzhou, China.
Meiosis in mammalian oocytes is interrupted by a prolonged arrest at the germinal vesicle stage, during which oocytes have to repair DNA lesions to ensure genome integrity or otherwise undergo apoptosis. The FIRRM/FLIP-FIGNL1 complex dissociates RAD51 from the joint DNA molecules in both homologous recombination (HR) and DNA replication. However, as a type of non-meiotic, non-replicative cells, whether this RAD51-dismantling mechanism regulates genome integrity in oocytes remains elusive.
View Article and Find Full Text PDFAssociation Between Serum Folate Concentrations and 10-Year Stroke Risk in a Prospective Community Cohort: Mediation and Interaction Analyses.
Nutrients
December 2024
Department of Cardiology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China.
The relationship between folate concentrations and stroke risk remains unestablished, and the mediation effect of homocysteine (Hcy) and interaction effect of methylenetetrahydrofolate reductase () gene polymorphism has yet to be investigated. This cohort study involved 4903 subjects derived from a Chinese community population. The association between folate and first stroke was examined in Cox proportional hazard regression models.
View Article and Find Full Text PDFIndividual and Joint Associations Between Animal and Plant Protein Intakes with Impaired Fasting Glucose and Type 2 Diabetes in the Framingham Offspring Study.
Nutrients
December 2024
Preventive Medicine and Epidemiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA.
Objectives: Given the considerable discrepancy in the literature regarding dietary protein and glucose homeostasis, we examined the prospective association between protein intake (total, animal, plant) and risk of type 2 diabetes mellitus or impaired fasting glucose (IFG). We also examined whether these associations differed by sex, body weight, or other risk factors.
Methods: We included 1423 subjects, aged ≥ 30 years, in the Framingham Offspring Study cohort.
The Health Effects of Dietary Nitrate on Sarcopenia Development: Prospective Evidence from the UK Biobank.
Foods
December 2024
Vanke School of Public Health, Tsinghua University, Beijing 100084, China.
Nitrate is abundant in natural foods, especially plant-based foods, having the potential to enhance muscle function. However, its relationship with sarcopenia in the context of daily diet remains unexplored. This cohort study investigated the associations between dietary nitrate intake and sarcopenia, as well as related symptoms, using data including 28,229 participants with a mean follow-up of 9.
View Article and Find Full Text PDFLigand-Independent Vitamin D Receptor Actions Essential for Keratinocyte Homeostasis in the Skin.
Int J Mol Sci
January 2025
Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Toyama, Japan.
Recently, we demonstrated that the alopecia observed in vitamin D receptor gene-deficient (-KO) rats is not seen in rats with a mutant VDR(R270L/H301Q), which lacks ligand-binding ability, suggesting that the ligand-independent action of VDR plays a crucial role in maintaining the hair cycle. Since -KO rats also showed abnormalities in the skin, the relationship between alopecia and skin abnormalities was examined. To clarify the mechanism of actions of vitamin D and VDR in the skin, protein composition, and gene expression patterns in the skin were compared among -KO, -R270L/H301Q, and wild-type (WT) rats.
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!