Activating transcription factor 3 mediates apoptotic functions through a p53-independent pathway in human papillomavirus 18 infected HeLa cells

Kooti, Abolfazl; Abuei, Haniyeh; Farhadi, Ali; Behzad-Behbahani, Abbas; Zarrabi, Maryam

doi:10.1007/s11262-022-01887-8

Cited by 6 publications

(7 citation statements)

References 47 publications

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“…In accordance with the mentioned studies, we found that the ectopic expression of ATF3 in Ca Ski cells increased the percentage of Ca Ski cells in the G1 phase of cell cycle which led to cell cycle arrest and apoptotic cell death. While in our previous study, we demonstrated that the percentage of HPV18-infected cells in the G1 phase was 43.2% after optimum transfection with the plasmid expressing ATF3-GFP in 48 h [ 27 ], in the present study, it has been revealed and that 66.7% of HPV16-infected cells were arrested in G1 phase which implies that the anticancer effects of ATF3 are dramatically more vigorous in HPV16-infected Ca Ski cells than in HPV18-infected HeLa cells. Apparently, ATF3 induces apoptosis and cell arrest through various pathways in cervical cancer cells based on the type of HPV infection involved.…”

Section: Discussionmentioning

confidence: 98%

“…Apparently, ATF3 induces apoptosis and cell arrest through various pathways in cervical cancer cells based on the type of HPV infection involved. Previously, we showed that in HPV18-infected HeLa cells, ATF3 functioned as a tumor suppressor factor through a p53‑independent pathway which induced apoptosis in the cells with depleted levels of p53 [ 27 ]. However, in the case of HPV16 infection, it has been shown that ATF3 competes with E6AP for direct binding to E6, suppresses E6-mediated p53 degradation, and thus restores p53 activity by blocking the recruitment of the ubiquitin ligase to p53, leading to diminished ubiquitination and proteolysis of the latter protein [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…The amplification and insertion of ATF3 into the pCMV6-AC-IRES-GFP vector and the construction of GFP-expressing pCMV6-ATF3 recombinant plasmid were performed according to the previously described method [ 27 ]. After transformation into E. coli DH5α competent cells purchased from the national cell bank of Iran (Pasteur Institute, Tehran, Iran), enzyme digestion, colony PCR, and Sanger sequencing were used to validate the recombinant plasmid.…”

Section: Methodsmentioning

confidence: 99%

“…In our previous study, we demonstrated that ATF3 acts as a tumor suppressor factor in HPV18-related cervical cancer cells which mediates apoptotic functions through a p53-independent pathway [ 27 ]. However, it was unknown whether ATF3 stimulates or represses tumorigenesis in HPV16-infected cells.…”

Section: Introductionmentioning

confidence: 99%

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Activating transcription factor 3 inhibits NF‑κB p65 signaling pathway and mediates apoptosis and cell cycle arrest in cervical cancer cells

Arsanjani

Abuei

Behzad-Behbahani

et al. 2022

Infect Agents Cancer

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Background As a novel tumor suppressor mediator, activating transcription factor 3 (ATF3) has recently aroused an interest in its possible therapeutic applications in various cancers. In this study, we evaluated the effect of ATF3 overexpression on the cellular level of nuclear factor kappa B (NF-κB) in human papillomavirus (HPV)-infected Ca Ski cells. Further, we examined whether ATF3 could mediate cell cycle arrest and alter the apoptosis level of Ca Ski cells. Methods The biological behavior of Ca Ski cells was evaluated prior and subsequent to the overexpression of ATF3 by MTT assay, fluorescence microscopy, cell cycle and annexin V/PI flow cytometric analysis. The effect of ectopic ATF3 expression on the cellular level of NF-κB in HPV-positive cells was evaluated by western blotting assay. Results The overexpression of ATF3 in Ca Ski cells led to significant apoptosis and cell cycle arrest in the G1 phase. Western blotting assay revealed a discernible reduction of NF-κB p65 level in cervical cancer cells. Conclusion ATF3 acts as a tumor suppressor factor in HPV16-infected Ca Ski cells and exerts anti-cancer effects on HPV16-related cervical cancer cells potentially by hindering cell growth and inducing cell cycle arrest through the down-regulation of NF-κB. Our results suggest that ATF3 induction or NF-κB suppression may be useful targets for HPV16-related cervical cancer prevention and treatment.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activating transcription factor 3 inhibits NF‑κB p65 signaling pathway and mediates apoptosis and cell cycle arrest in cervical cancer cells

Arsanjani

Abuei

Behzad-Behbahani

et al. 2022

Infect Agents Cancer

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“…HPV facilitates the proteolytic degradation and inactivation of p53 through the expression of the E6 protein [136,137]. Therefore, inhibiting the E6-promoted degradation of p53 appears to be an effective intervention against HPV-induced cervical cancer [137][138][139].…”

Section: Dna Virusmentioning

confidence: 99%

The Dual Roles of Activating Transcription Factor 3 (ATF3) in Inflammation, Apoptosis, Ferroptosis, and Pathogen Infection Responses

Liu,

Li,

Lan

et al. 2024

IJMS

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Transcription factors are pivotal regulators in the cellular life process. Activating transcription factor 3 (ATF3), a member of the ATF/CREB (cAMP response element-binding protein) family, plays a crucial role as cells respond to various stresses and damage. As a transcription factor, ATF3 significantly influences signal transduction regulation, orchestrating a variety of signaling pathways, including apoptosis, ferroptosis, and cellular differentiation. In addition, ATF3 serves as an essential link between inflammation, oxidative stress, and immune responses. This review summarizes the recent advances in research on ATF3 activation and its role in regulating inflammatory responses, cell apoptosis, and ferroptosis while exploring the dual functions of ATF3 in these processes. Additionally, this article discusses the role of ATF3 in diseases related to pathogenic microbial infections. Our review may be helpful to better understand the role of ATF3 in cellular responses and disease progression, thus promoting advancements in clinical treatments for inflammation and oxidative stress-related diseases.

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Activation of ATF3 via the Integrated Stress Response Pathway Regulates Innate Immune Response to Restrict Zika Virus

Badu

Pager

2023

Preprint

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

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Activating transcription factor 3 mediates apoptotic functions through a p53-independent pathway in human papillomavirus 18 infected HeLa cells

Cited by 6 publications

References 47 publications

Activating transcription factor 3 inhibits NF‑κB p65 signaling pathway and mediates apoptosis and cell cycle arrest in cervical cancer cells

Activating transcription factor 3 inhibits NF‑κB p65 signaling pathway and mediates apoptosis and cell cycle arrest in cervical cancer cells

The Dual Roles of Activating Transcription Factor 3 (ATF3) in Inflammation, Apoptosis, Ferroptosis, and Pathogen Infection Responses

Activation of ATF3 via the Integrated Stress Response Pathway Regulates Innate Immune Response to Restrict Zika Virus

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