ArticlePloS one2018
Implication of KRT16, FAM129A and HKDC1 genes as ATF4 regulated components of the integrated stress response.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
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- A bioinformatic analysis found low expression and clinical significance of ATF4 in breast cancer.Heliyon · 2024Article
- Research progress and application of single-cell sequencing in head and neck malignant tumors.Cancer gene therapy · 2024Review
- Aiding Cancer's "Sweet Tooth": Role of Hexokinases in Metabolic Reprogramming.Life (Basel, Switzerland) · 2023Review
- The pan-cancer landscape of abnormal DNA methylation and intratumor microorganisms.Neoplasia (New York, N.Y.) · 2023Article
- Transcriptomic Analysis of Circulating Leukocytes Obtained during the Recovery from Clinical Mastitis Caused byAnimals : an open access journal from MDPI · 2022Article
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- Hexokinase domain-containing protein-1 in metabolic diseases and beyond.Trends in endocrinology and metabolism: TEM · 2022Review
- The Role of Hexokinase Domain Containing Protein-1 in Glucose Regulation During Pregnancy.Current diabetes reports · 2021Review
- The Regulatory Role of GBF1 on Osteoclast Activation Through EIF2a Mediated ER Stress and Novel Marker FAM129A Induction.Frontiers in cell and developmental biology · 2021Article
- The Effects of Lentivirus-Mediated Gene Silencing ofJournal of Cancer · 2021Article
- Exploratory Genome-Wide Interaction Analysis of Nonsteroidal Anti-inflammatory Drugs and Predicted Gene Expression on Colorectal Cancer Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Article
- A cell permeant phosphopeptide mimetic of Niban inhibits p38 MAPK and restores endothelial function after injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Transcriptome analysis of HPV-induced warts and healthy skin in humans.BMC medical genomics · 2020Article
- Genes Regulated by HPV 16 E6 and High Expression of NFX1-123 in Cervical Cancers.OncoTargets and therapy · 2020Article
- Utility of Extrapolating Human S1500+ Genes to the Whole Transcriptome: Tunicamycin Case Study.Bioinformatics and biology insights · 2020Article
- Age modulates liver responses to asparaginase-induced amino acid stress in mice.The Journal of biological chemistry · 2019Article
- Regulation of the unfolded protein response through ATF4 and FAM129A in prostate cancer.Oncogene · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ATF4 transcription factor is a key regulator of the adaptive integrated stress response (ISR) induced by various stresses and pathologies. Identification of novel transcription targets of ATF4 during ISR would contribute to the understanding of adaptive networks and help to identify novel therapeutic targets. We were previously searching for genes that display an inverse regulation mode by the transcription factors ATF4 and p53 in response to mitochondrial respiration chain complex III inhibition. Among the selected candidates the human genes for cytokeratine 16 (KRT16), anti-apoptotic protein Niban (FAM129A) and hexokinase HKDC1 have been found highly responsive to ATF4 overexpression. Here we explored potential roles of the induction of KRT16, FAM129A and HKDC1 genes in ISR. As verified by RT-qPCR, a dysfunction of mitochondrial respiration chain and ER stress resulted in a partially ATF4-dependent stimulation of KRT16, FAM129A and HKDC1 expression in the HCT116 colon carcinoma cell line. ISRIB, a specific inhibitor of ISR, was able to downregulate the ER stress-induced levels of KRT16, FAM129A and HKDC1 transcripts. An inhibition of ATF4 by RNAi attenuated the induction of KRT16, FAM129A and HKDC1 mRNAs in response to ER stress or to a dysfunctional mitochondrial respiration. The similar induction of the three genes was observed in another tumor-derived cervical carcinoma cell line HeLa. However, in HaCaT and HEK293T cells that display transformed phenotypes, but do not originate from patient-derived tumors, the ER stress-inducing treatments resulted in an upregulation of FAM129A and HKDC1, but not KRT16 transcripts, By a luciferase reporter approach we identified a highly active ATF4-responsive element within the upstream region of the KRT16 gene. The results suggest a conditional regulation of KRT16 gene by ATF4 that may be inhibited in normal cells, but engaged during cancer progression. Potential roles of KRT16, FAM129A and HKDC1 genes upregulation in adaptive stress responses and pathologies are discussed.
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