A Csde1-Strap complex regulates plasma cell differentiation by coupling mRNA translation and decay DOI Creative Commons

Pengda Chen,

Lianghua Lin,

Xinyong Lin

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 25, 2025

Upon encountering antigens, B cells may undergo multiple differentiation paths, including becoming plasma and memory cells. Although it is well-known that transcription factors govern gene expression programs underpinning these fate decisions in transcriptional level, the role of post-transcriptional regulators, with a focus on RNA-binding proteins, determination are lesser known. Here we find by RNA interactome capture-coupled CRISPR/Cas9 functional screening Csde1-Strap complex plays an important cell differentiation. Mechanistically, establishes kinetics Bach2, key regulator Bach2 rapidly induced to promote expansion then decreased initiate The interaction critical for their binding mRNA couple its decay translation restrain magnitude duration protein expression. In absence Csde1 or Strap, de-coupled from decay, leading elevated prolonged impaired This study thus RBP landscape illustrates fundamental importance controlling determination. Plasma governed program, which regulators mostly known but other regulatory elements, such as proteins remain explored. authors show complex, Csde1-Strap, regulates window expression, factor necessary transient preceding differentiation, via coupling decay.

Language: Английский

Rethinking transcription factor dynamics and transcription regulation in eukaryotes DOI
Reiner A. Veitia

Trends in Biochemical Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Role Of Critical Molecules In Proliferation and Apoptosis In Tumoral And Peri-Tumoral Microenvironments Of Gastric Cancer DOI Creative Commons
Venhar Çınar, Zühal Hamurcu, Dilara Sönmez

et al.

Pharmedicine journal., Journal Year: 2025, Volume and Issue: 2(1), P. 24 - 30

Published: Feb. 28, 2025

Introduction: Gastric cancers (GC) are one of the main causes cancer-related deaths worldwide. Despite dizzying progress in diagnostic and therapeutic strategies, many GC cases diagnosed at advanced stages. Various signaling pathways have been identified to play vital roles GC. Although importance these has demonstrated, further clinical studies needed. Therefore, expression some proteins tumoral peri-tumoral microenvironments examined this study. Methods: Protein levels were analyzed using Western blotting method tumor non-tumorous tissues from nine sufferers. The Kaplan-Meier was used for log-rank test estimate survival curves examine distribution. Results: It found that overexpression c-MYC, mTOR, AKT alongside decreased degrees AMPK TRAIL tissues. analysis highlighted worse outcomes patients with high mTOR expression, while associated improved survival. Interestingly, a poorer prognosis higher c-MYC highlighting oncogenic role protein through AKT/mTOR pathway. On other hand, implied lack tumor-suppressive properties, most likely due activation. Conclusion: These highlight intricate interplay between GC's carcinogenic mechanisms. Targeting molecules by inhibiting or activating may provide new treatment approaches which can significantly increase sensitivity. Moreover, necessary confirm present results establish integrated therapy approaches.

Language: Английский

Citations

0
Discovery of a Pyrazolopyridinone-Based MYC Inhibitor That Selectively Engages Intracellular c-MYC and Disrupts MYC–MAX Heterodimerization DOI
Oluwatosin A. Obisesan, Samuel Ofori,

Owamagbe N. Orobator

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

c-MYC is an oncogenic transcription factor that plays a crucial role in the regulation of downstream targets involved proliferation, apoptosis, differentiation, metabolism, signaling, and immune response processes whose deregulation leads to progression different pathologies. The development selective potent small-molecule inhibitors remains grand challenge chemical biology medicine due its undruggability, derived from extensive intrinsic disorder. In this study, we identified novel dihydro pyrazolo pyridinone scaffold, MY05, selectively cells disrupts MYC-MAX interaction. MY05 engages intracellular c-MYC, modulates thermal stability, reduces transcriptional targets, inhibits proliferation cancer tumor growth mice. summary, compound directly interacts with disrupt program.

Language: Английский

Citations

0
The Role of Non-Coding RNAs in MYC-Mediated Metabolic Regulation: Feedback Loops and Interactions DOI Creative Commons
Aliaa A. Alamoudi

Non-Coding RNA, Journal Year: 2025, Volume and Issue: 11(2), P. 27 - 27

Published: March 18, 2025

Metabolic reprogramming is a hallmark of cancer, crucial for supporting the rapid energy demands tumor cells. MYC, often deregulated and overexpressed, key driver this shift, promoting Warburg effect by enhancing glycolysis. However, there remains gap in understanding mechanisms factors influencing MYC's metabolic roles. Recently, non-coding RNAs (ncRNAs) have emerged as important modulators MYC functions. This review focuses on ncRNAs that regulate MYC-driven metabolism, particularly effect. The categorizes these into three main groups based their interaction with examines behind interactions. Additionally, we explore how different types may collaborate or influence each other's roles regulation function, aiming to identify biomarkers synthetic lethality targets disrupt cancer. Finaly, highlights clinical implications ncRNAs, providing an up-to-date summary potential cancer prognosis therapy. With recent advances MYC-targeted therapy reaching trials, exciting combining therapies ncRNA-based strategies holds great promise treatment efficacy.

Language: Английский

Citations

0
A Csde1-Strap complex regulates plasma cell differentiation by coupling mRNA translation and decay DOI Creative Commons

Pengda Chen,

Lianghua Lin,

Xinyong Lin

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 25, 2025

Upon encountering antigens, B cells may undergo multiple differentiation paths, including becoming plasma and memory cells. Although it is well-known that transcription factors govern gene expression programs underpinning these fate decisions in transcriptional level, the role of post-transcriptional regulators, with a focus on RNA-binding proteins, determination are lesser known. Here we find by RNA interactome capture-coupled CRISPR/Cas9 functional screening Csde1-Strap complex plays an important cell differentiation. Mechanistically, establishes kinetics Bach2, key regulator Bach2 rapidly induced to promote expansion then decreased initiate The interaction critical for their binding mRNA couple its decay translation restrain magnitude duration protein expression. In absence Csde1 or Strap, de-coupled from decay, leading elevated prolonged impaired This study thus RBP landscape illustrates fundamental importance controlling determination. Plasma governed program, which regulators mostly known but other regulatory elements, such as proteins remain explored. authors show complex, Csde1-Strap, regulates window expression, factor necessary transient preceding differentiation, via coupling decay.

Language: Английский

Citations

0