PTEN (phosphatase and tensin homolog), a tumor suppressor frequently mutated in human cancer, has various cytoplasmic and nuclear functions. PTEN translocates to the nucleus from the cytoplasm in response to oxidative stress. However, the mechanism and function of the translocation are not completely understood. In this study, topotecan (TPT), a topoisomerase I inhibitor, and cisplatin (CDDP) were employed to induce DNA damage. The results indicate that TPT or CDDP activates ATM (ATM serine/threonine kinase), which phosphorylates PTEN at serine 113 and further regulates PTEN nuclear translocation in A549 and HeLa cells. After nuclear translocation, PTEN induces autophagy, in association with the activation of the p-JUN-SESN2/AMPK pathway, in response to TPT. These results identify PTEN phosphorylation by ATM as essential for PTEN nuclear translocation and the subsequent induction of autophagy in response to DNA damage.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502816 | PMC |
http://dx.doi.org/10.1080/15548627.2015.1009767 | DOI Listing |
Nat Commun
January 2025
Institute for Stem Cell & Regenerative Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, 710004, Xi'an, China.
Blood clots (BCs) play a crucial biomechanical role in promoting osteogenesis and regulating mesenchymal stem cell (MSC) function and fate. This study shows that BC formation enhances MSC osteogenesis by activating Itgb1/Fak-mediated focal adhesion and subsequent Runx2-mediated bone regeneration. Notably, BC viscoelasticity regulates this effect by modulating Runx2 nuclear translocation.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
January 2025
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, China; Department of Cariology and Endodontology, School & Hospital of Stomatology, Wuhan University, China. Electronic address:
BRCA1/BRCA2-containing complex subunit 3 (BRCC3) has been proved to exert pro-inflammatory effect in various inflammatory diseases through different mechanisms, but its involvement in pulpitis remains unclear. This study aims to investigate the regulatory role and mechanisms of BRCC3 in modulating dental pulp cell inflammation and pulpitis progression. The expression of BRCC3 was observed to be elevated in human/mouse pulpitis samples and lipopolysaccharide-stimulated human dental pulp cells (hDPCs).
View Article and Find Full Text PDFJ Neurotrauma
January 2025
Department of Neurosurgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China.
Following traumatic brain injury (TBI), inhibition of the Na-K-Cl cotransporter1 (NKCC1) has been observed to alleviate damage to the blood-brain barrier (BBB). However, the underlying mechanism for this effect remains unclear. This study aimed to investigate the mechanisms by which inhibiting the NKCC1 attenuates disruption of BBB integrity in TBI.
View Article and Find Full Text PDFiScience
February 2025
Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Human herpesvirus 6B (HHV-6B) belongs to the genus of the betaherpesvirus subfamily, causing exanthema subitum and encephalitis. Although viral ribonucleotide reductase (RNR) is conserved in betaherpesviruses, it has lost its enzymatic activity. Human cytomegalovirus (HCMV) belongs to the other betaherpesvirus genus, ; its RNR inhibits nuclear factor-kappa B (NF-κB) signaling via interaction with the adaptor molecule RIPK1.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Department of Gastroenterology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
Introduction: Ulcerative colitis (UC), a form of inflammatory irritable bowel disease, is characterized by a recurrent and persistent nonspecific inflammatory response. Polydatin (PD), a natural stilbenoid polyphenol with potent properties, exhibits unexpected beneficial effects beyond its well-documented anti-inflammatory and antioxidant activities. In this study, we presented evidence that PD confers protection against dextran sodium sulfate (DSS)-induced ulcerative colitis.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!