ATF family members as therapeutic targets in cancer: From mechanisms to pharmacological interventions DOI Creative Commons

Xueyao Zhang,

Zhijia Li, Xiaochun Zhang

и другие.

Pharmacological Research, Год журнала: 2024, Номер 208, С. 107355 - 107355

Опубликована: Авг. 22, 2024

The activating transcription factor (ATF)/ cAMP-response element binding protein (CREB) family represents a large group of basic zone leucine zip (bZIP) factors (TFs) with variety physiological functions, such as endoplasmic reticulum (ER) stress, amino acid heat oxidative integrated stress response (ISR) and thus inducing cell survival or apoptosis. Interestingly, ATF has been increasingly implicated in autophagy ferroptosis recent years. Thus, the is important for homeostasis its dysregulation may promote disease progression including cancer. Current therapeutic approaches to modulate include direct modulators, upstream post-translational modifications (PTMs) modulators. This review summarizes structural domain PTMs feature ATF/CREB comprehensively explores molecular regulatory mechanisms. On this basis, their pathways affecting proliferation, metastasis, drug resistance various types cancer cells are sorted out discussed. We then systematically summarize status applications existing modulators finally look forward future prospect clinical treatment tumors by modulating family.

Язык: Английский

Polystyrene microplastics induce activation and cell death of neutrophils through strong adherence and engulfment DOI Creative Commons

Koung-Min Park,

Bora Kim,

Wonjin Woo

и другие.

Journal of Hazardous Materials, Год журнала: 2024, Номер 480, С. 136100 - 136100

Опубликована: Окт. 11, 2024

Ingested microplastics (MPs) can accumulate throughout whole body, which may induce the dysfunction of immune system. However, it remains unclear how MP exposure affects innate responses at cellular level. We found that mouse neutrophils strongly bind and then engulf polystyrene MPs. This interaction leads to proinflammatory state eventually results in apoptotic cell death through toll-like receptor signaling pathway a bacteria-recognition mimetic manner. Moreover, our data verified orally administered MPs reach various organs mice, where they are interacted with endocytosed by neutrophils. confirmed human also internalize Additionally, RNA sequencing analysis MPs-exposed showed upregulation death-related function. Therefore, accumulated exacerbate inflammatory response disrupting neutrophil These provide novel insight into adverse induced exposure.

Язык: Английский

Процитировано

2
Activation of ATF3 via the Integrated Stress Response Pathway Regulates Innate Immune Response to Restrict Zika Virus DOI Creative Commons
Pheonah Badu, Gabriele Baniulyte, Morgan A. Sammons

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июль 27, 2023

Zika virus (ZIKV) is a re-emerging mosquito-borne flavivirus that can have devastating health consequences. The developmental and neurological effects from ZIKV infection arise in part the triggering cellular stress pathways perturbing transcriptional programs. To date, underlying mechanisms of control directing viral restriction virus-host interaction are understudied. Activating Transcription Factor 3 (ATF3) stress-induced effector modulates expression genes involved myriad processes, including inflammation antiviral responses, to restore homeostasis. While ATF3 known be upregulated during infection, mode by which activated specific role unknown. In this study, we show via inhibitor RNA interference approaches initiates integrated response pathway activate ATF4 turn induces expression. Additionally, using CRISPR-Cas9 system delete ATF3, found acts limit gene A549 cells. We also determined enhances such as STAT1 other components innate immunity induce an ATF3-dependent anti-ZIKV response. Our study reveals crosstalk between immune highlights important for establishing effect infection.

Язык: Английский

Процитировано

5
Zika virus infection in a cell culture model reflects the transcriptomic signatures in patients. DOI Creative Commons

Gillian Berglund,

Claudia D. Lennon,

Pheonah Badu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 25, 2024

Zika virus (ZIKV), a re-emerging flavivirus, is associated with devasting developmental and neurological disease outcomes particularly in infants infected

Язык: Английский

Процитировано

1
Knockdown of DJ-1 Resulted in a Coordinated Activation of the Innate Immune Antiviral Response in HEK293 Cell Line DOI Open Access
Keren Zohar, Michal Linial

Опубликована: Июнь 24, 2024

PARK7, also known as DJ-1, plays a critical role in protecting cells by functioning sensitive oxidation sensor and modulator of antioxidants. DJ-1 acts to maintain mitochondrial function regulate transcription response different stressors. In this study, we showed that cell lines vary based on their antioxidation potential at basal conditions. The transcriptome HEK293 was tested following knockdown (KD) using siRNAs which reduced the transcripts only 12% original level. We compared expression levels 14k protein-coding transcripts, 4.2k non-coding RNAs relative control treated with non-specific siRNAs. Among coding genes, ~200 upregulated differentially expressed genes (DEGs) signified coordinated antiviral innate immune response. Most were associated regulation type 1 interferons (IFN) induction inflammatory cytokines. About quarter these induced used negative control. Beyond response, 114 specific KD enrichment RNA metabolism functions. A smaller set downregulated (58 genes) dysregulation membrane structure, viability, mitophagy. propose diminish its protective potency against oxidative stress, rendering labile responsive dsRNA signal activation large number many drive apoptosis, death, signatures. highlights crucial regulating responses, metabolism, functions, apparently through alteration STAT activity downstream signaling. Given is highly metastatic cancers, targeting could be promising therapeutic strategy where manipulation may reduce cancer viability enhance efficacy treatments.

Язык: Английский

Процитировано

1
ATF family members as therapeutic targets in cancer: From mechanisms to pharmacological interventions DOI Creative Commons

Xueyao Zhang,

Zhijia Li, Xiaochun Zhang

и другие.

Pharmacological Research, Год журнала: 2024, Номер 208, С. 107355 - 107355

Опубликована: Авг. 22, 2024

The activating transcription factor (ATF)/ cAMP-response element binding protein (CREB) family represents a large group of basic zone leucine zip (bZIP) factors (TFs) with variety physiological functions, such as endoplasmic reticulum (ER) stress, amino acid heat oxidative integrated stress response (ISR) and thus inducing cell survival or apoptosis. Interestingly, ATF has been increasingly implicated in autophagy ferroptosis recent years. Thus, the is important for homeostasis its dysregulation may promote disease progression including cancer. Current therapeutic approaches to modulate include direct modulators, upstream post-translational modifications (PTMs) modulators. This review summarizes structural domain PTMs feature ATF/CREB comprehensively explores molecular regulatory mechanisms. On this basis, their pathways affecting proliferation, metastasis, drug resistance various types cancer cells are sorted out discussed. We then systematically summarize status applications existing modulators finally look forward future prospect clinical treatment tumors by modulating family.

Язык: Английский

Процитировано

1