Piperlongumine overcomes osimertinib resistance via governing ubiquitination-modulated Sp1 turnover DOI Creative Commons
Ruirui Wang, Qiang Wang, Jinzhuang Liao

et al.

JCI Insight, Journal Year: 2025, Volume and Issue: 10(6)

Published: March 23, 2025

Non-small cell lung cancer (NSCLC) is a common cause of cancer-related deaths worldwide, and its incidence has been increasing in recent years. While targeted therapies like osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor, have brought about notable improvements patient outcomes for advanced NSCLC, the challenge acquired drug resistance persists. Here, we found that cellular mesenchymal-epithelial transition (c-Met) was highly expressed osimertinib-resistant cells, depletion c-Met markedly inhibited cells ex vivo vivo, suggesting potential target to address osimertinib resistance. Through screening process using natural product compound library, identified piperlongumine as potent inhibitor overcome Furthermore, combined treatment exhibited robust antitumor effects resistant partially restoring their sensitivity osimertinib. Additionally, discovered could enhance interaction between E3 ligase RNF4 Sp1, inhibit phosphorylation Sp1 at Thr739, facilitate ubiquitination degradation lead destabilization, trigger intrinsic apoptosis cells. In summary, our study sheds light on overcoming resistance, offering new strategies perspectives clinical management drug-resistant NSCLC.

Language: Английский

Transcription factor specificity protein (SP) family in renal physiology and diseases DOI Creative Commons
Weitao Zhou,

Jiaxi Fang,

Qingqing Jia

et al.

PeerJ, Journal Year: 2025, Volume and Issue: 13, P. e18820 - e18820

Published: Jan. 20, 2025

Dysregulated specificity proteins (SPs), members of the C2H2 zinc-finger family, are crucial transcription factors (TFs) with implications for renal physiology and diseases. This comprehensive review focuses on role SP family members, particularly SP1 SP3, in pathology. A detailed analysis their expression cellular localization healthy human kidney is presented, highlighting involvement fatty acid metabolism, electrolyte regulation, synthesis important molecules. The also delves into diverse roles SPs various diseases, including ischemia/reperfusion injury, diabetic nephropathy, interstitial fibrosis, lupus nephritis, elucidating molecular mechanisms potential as therapeutic targets. further discusses pharmacological modulation its treatment. Our findings provide a understanding health disease, offering new avenues targeted interventions precision medicine nephrology.

Language: Английский

Citations

0
Viral Appropriation of Specificity Protein 1 (Sp1): The Role of Sp1 in Human Retro- and DNA Viruses in Promoter Activation and Beyond DOI Creative Commons

Kira Sviderskaia,

Vanessa Meier‐Stephenson

Viruses, Journal Year: 2025, Volume and Issue: 17(3), P. 295 - 295

Published: Feb. 20, 2025

Specificity protein 1 (Sp1) is a highly ubiquitous transcription factor and one employed by numerous viruses to complete their life cycles. In this review, we start summarizing the relationships between Sp1 function, DNA binding, structural motifs. We then describe role plays in transcriptional activation of seven viral families, composed human retro- viruses, with focus on key promoter regions. Additionally, discuss pathways common across multiple highlighting importance cell regulatory Sp1. also Sp1-related epigenetic post-translational modifications during infection how they relate binding. Finally, these insights mind, comment potential for Sp1-targeting therapies, such as repurposing drugs currently use anti-cancer realm, what limitations agents would have antivirals.

Language: Английский

Citations

0
Piperlongumine overcomes osimertinib resistance via governing ubiquitination-modulated Sp1 turnover DOI Creative Commons
Ruirui Wang, Qiang Wang, Jinzhuang Liao

et al.

JCI Insight, Journal Year: 2025, Volume and Issue: 10(6)

Published: March 23, 2025

Non-small cell lung cancer (NSCLC) is a common cause of cancer-related deaths worldwide, and its incidence has been increasing in recent years. While targeted therapies like osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor, have brought about notable improvements patient outcomes for advanced NSCLC, the challenge acquired drug resistance persists. Here, we found that cellular mesenchymal-epithelial transition (c-Met) was highly expressed osimertinib-resistant cells, depletion c-Met markedly inhibited cells ex vivo vivo, suggesting potential target to address osimertinib resistance. Through screening process using natural product compound library, identified piperlongumine as potent inhibitor overcome Furthermore, combined treatment exhibited robust antitumor effects resistant partially restoring their sensitivity osimertinib. Additionally, discovered could enhance interaction between E3 ligase RNF4 Sp1, inhibit phosphorylation Sp1 at Thr739, facilitate ubiquitination degradation lead destabilization, trigger intrinsic apoptosis cells. In summary, our study sheds light on overcoming resistance, offering new strategies perspectives clinical management drug-resistant NSCLC.

Language: Английский

Citations

0