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

The heterogeneity of neutrophils in cancer and its implication for therapeutic targeting DOI
Evgeniy Eruslanov, Yulia Nefedova, Dmitry I. Gabrilovich

и другие.

Nature Immunology, Год журнала: 2025, Номер 26(1), С. 17 - 28

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

2
Isoliquiritigenin alleviates neuropathic pain by reducing microglia inflammation through inhibition of the ERK signaling pathway and decreasing CEBPB transcription expression DOI Creative Commons
Zikun Wang, Shu Jia, Xiaozheng Kang

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 143, С. 113536 - 113536

Опубликована: Ноя. 2, 2024

Язык: Английский

Процитировано

5
Gasoline exhaust particles induce MMP1 expression via Nox4-derived ROS-ATF3-linked pathway in human umbilical vein endothelial cells DOI
Gi‐Young Kim, Suji Kim, Kihong Park

и другие.

Toxicology, Год журнала: 2025, Номер unknown, С. 154051 - 154051

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Toll-Like Receptors in Kidney Ischemia-Reperfusion Injury: Modulating Macrophage Responses for Therapeutic Insights DOI

H. Malathi,

Gaurav Khandelwal,

S. Gayathri

и другие.

Pathology - Research and Practice, Год журнала: 2025, Номер unknown, С. 155940 - 155940

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Estradiol activates the CaMKKβ/AMPK pathway to enhance neurite outgrowth in cultured adult sensory neurons DOI Creative Commons
Pranav Mishra, Benedict C. Albensi, Paul Fernyhough

и другие.

Molecular and Cellular Neuroscience, Год журнала: 2025, Номер unknown, С. 104008 - 104008

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
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.

Journal of Virology, Год журнала: 2024, Номер unknown

Опубликована: Авг. 30, 2024

ABSTRACT Zika virus (ZIKV) is a re-emerging mosquito-borne flavivirus that can have devastating health consequences. The developmental and neurological effects of ZIKV infection arise in part from the triggering cellular stress pathways perturbing transcriptional programs. To date, underlying mechanisms 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. IMPORTANCE co-opts support processes reprogram host profile. Such viral-directed changes pro- or anti-viral outcomes remain previously showed transcription factor, significantly ZIKV-infected mammalian cells, along with genes. now define intracellular responsible activation elucidate impact on stimulates antagonize This establishes link viral-induced regulation defense thus expands our knowledge virus-mediated interferon-stimulated

Язык: Английский

Процитировано

4
Activating transcription factor‐3 orchestrates the modulation of vascular anti‐contractile activity and relaxation by governing the secretion of HDL‐bound sphingosine‐1‐phosphate in perivascular adipose tissue DOI Open Access

Hsiao‐Fen Li,

Heng Lin,

Hsin‐Tzu Liu

и другие.

British Journal of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Abstract Background and Purpose Perivascular adipose tissues (PVATs) play a critical role in modulating vascular homeostasis protecting against cardiovascular dysfunction‐mediated blood pressure dysregulation. We demonstrated that the activating transcription factor‐3 ( Atf3 ) gene PVAT is crucial for improving wall tension abnormalities; however, its protective mechanism remains unclear. Herein, we aim to determine whether ATF3 regulates PVAT‐derived relaxing factor (PVDRF) biosynthesis if secretion contributes vasorelaxation. Experimental Approach This study employed an vivo animal model using global ‐deficient mice, vitro vessel myography, biochemical analyses evaluate ATF3‐mediated PVDRF release reactivity vasculature. Key Results Wild‐type (WT) mouse thoracic aortic extracts significantly induced resting tone dilation attenuated vasoconstrictor‐induced contractile responses compared −/− mice. Heat‐stable from WT mice caused sustained reproducible vasodilation without tachyphylaxis control rings. Biochemical evaluation of revealed had lower sphingosine‐1‐phosphate (S1P) HDL cholesterol (HDL‐C) levels than Furthermore, long‐lasting vasorelaxation, which was inhibited by S1P 3 receptor antagonist TY52156 scavenger class B type 1 glyburide. Conclusion Implications within can modulate function strengthening sphingosine kinase (sphk1)–S1P–S1P lipid signalling stimulating binding form vasodilator HDL‐S1P. essential modulator maintaining physiological PVAT, providing novel target treatment obesity‐related diseases.

Язык: Английский

Процитировано

0
Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11 DOI Creative Commons

Benjamin J. Ravenhill,

Marisa Oliveira,

G. J. Wood

и другие.

Cell Reports, Год журнала: 2025, Номер 44(2), С. 115263 - 115263

Опубликована: Фев. 1, 2025

Appropriate cellular recognition of viruses is essential for the generation an effective innate and adaptive immune response. Viral sensors their downstream signaling components thus provide a crucial first line host defense. Many them exhibit subcellular relocalization upon activation, resulting in expression interferon antiviral genes. To comprehensively identify factors, we analyzed protein on global scale during viral infection. cAMP-responsive element-binding (CREB)-regulated transcription coactivators 2 3 (CRTC2/3) exhibited early cytoplasmic-to-nuclear translocation infection with multiple diverse cell types. This movement was dependent mitochondrial (MAVS), cyclo-oxygenase proteins, kinase A. A key effect CRTC2/3 fibro-inflammatory cytokine interleukin (IL)-11. may be important clinically infections associated fibrosis, including SARS-CoV-2. Nuclear is, therefore, identified as pathway context

Язык: Английский

Процитировано

0
ATF3-SLC7A7 Axis Regulates mTORC1 Signaling to Suppress Lipogenesis and Tumorigenesis in Hepatocellular Carcinoma DOI Creative Commons
Qinglin Zhang,

Fengzhi Zhu,

Yin Tong

и другие.

Cells, Год журнала: 2025, Номер 14(4), С. 253 - 253

Опубликована: Фев. 11, 2025

Hepatocellular carcinoma (HCC) poses a substantial global health burden, with poor prognosis and high mortality rates. Dysregulated lipid metabolism has emerged as critical driver of HCC progression. While mTORC1 signaling is known to promote synthesis in HCC, the regulatory mechanisms governing remain largely unclear. Here, we demonstrate that inhibition significantly reduces lipogenesis uncover axis involving transcription factor ATF3 leucine–arginine transporter SLC7A7. Transcriptomic analysis patients reveals an inverse correlation between expression synthesis, finding corroborated by experimental validation. Mechanistically, suppresses signaling, thereby inhibiting biosynthesis, SLC7A7 identified key intermediary this process. Specifically, binds enhancer region SLC7A7, driving its transcriptional activation subsequently restraining activity. Functional assays ATF3-overexpressing -knockdown cell lines further confirm ATF3′s role tumor suppressor. Our study identifies novel ATF3-SLC7A7-mTORC1 attenuates tumorigenesis establishing link hepatocarcinogenesis. These findings offer new insights into potential therapeutic targets for treatment HCC.

Язык: Английский

Процитировано

0
The Effects of Vitamin D on Muscle Strength Are Influenced by Testosterone Levels DOI Creative Commons
Aolin Yang, Qingqing Lv, Zhongyan Han

и другие.

Journal of Cachexia Sarcopenia and Muscle, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 1, 2025

ABSTRACT Background Although the role of vitamin D receptor (VDR) in muscle mass and strength is well established, effects (VD) on remain controversial due to various factors. Herein, influence sex VD function underlying reasons was explored. Methods Male female Sod1 gene knockout (SKO) mice, serving as a model for skeletal atrophy, were treated with active analogue calcipotriol, RNA sequencing employed investigate this potential signalling pathway. The National Health Nutrition Examination Survey (NHANES) database utilized explore whether testosterone affects correlation between grip human participants. Experiments involving C2C12 cells castrated male mice subjected immobilization conducted demonstrate enhancing function. Results In SKO Vdr expression gastrocnemius positively correlated ( R 2 = 0.4689, p < 0.001), whereas no such identified mice. At 28 weeks age, both exhibited significantly reduced compared wild‐type (SWT) calcipotriol restored (SWT‐veh: 0.0716 ± 0.0006, SWT‐cal: 0.0686 0.0010, SKO‐veh: 0.0601 SKO‐cal: 0.0703 0.0007; 0.05). Calcipotriol increased protein synthesis mitochondrial biogenesis while decreasing inflammation atrogenes However, effect not significant Compared levels 1,25(OH) 3 ROS‐induced hepatic CYP3A4 overexpression, thereby excluding baseline levels. serum 25(OH)D interactively affect adults Using differentiated into myotubes, enhanced inducing VDR, androgen (AR), P‐AKT, PGC1α, Beclin1 LC3B. improved sham‐operated but had negligible improvement observed following restoration Conclusions This study demonstrates existence heterogeneity that enhances molecular responses VD. These findings underscore importance considering when utilizing enhance strength.

Язык: Английский

Процитировано

0