دورية أكاديمية

IFRD1 promotes tumor cells 'low-cost' survival under glutamine starvation via inhibiting histone H1.0 nucleophagy

التفاصيل البيبلوغرافية
العنوان: IFRD1 promotes tumor cells 'low-cost' survival under glutamine starvation via inhibiting histone H1.0 nucleophagy
المؤلفون: Yabin Huang, Fanzheng Meng, Taofei Zeng, Rick Francis Thorne, Lifang He, Qingrui Zha, Hairui Li, Hong Liu, Chuandong Lang, Wanxiang Xiong, Shixiang Pan, Dalong Yin, Mian Wu, Xuedan Sun, Lianxin Liu
المصدر: Cell Discovery, Vol 10, Iss 1, Pp 1-21 (2024)
بيانات النشر: Nature Publishing Group, 2024.
سنة النشر: 2024
المجموعة: LCC:Cytology
مصطلحات موضوعية: Cytology, QH573-671
الوصف: Abstract Glutamine addiction represents a metabolic vulnerability of cancer cells; however, effective therapeutic targeting of the pathways involved remains to be realized. Here, we disclose the critical role of interferon-related developmental regulator 1 (IFRD1) in the adaptive survival of hepatocellular carcinoma (HCC) cells during glutamine starvation. IFRD1 is induced under glutamine starvation to inhibit autophagy by promoting the proteasomal degradation of the key autophagy regulator ATG14 in a TRIM21-dependent manner. Conversely, targeting IFRD1 in the glutamine-deprived state increases autophagy flux, triggering cancer cell exhaustive death. This effect largely results from the nucleophilic degradation of histone H1.0 and the ensuing unchecked increases in ribosome and protein biosynthesis associated with globally enhanced chromatin accessibility. Intriguingly, IFRD1 depletion in preclinical HCC models synergizes with the treatment of the glutaminase-1 selective inhibitor CB-839 to potentiate the effect of limiting glutamine. Together, our findings reveal how IFRD1 supports the adaptive survival of cancer cells under glutamine starvation, further highlighting the potential of IFRD1 as a therapeutic target in anti-cancer applications.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2056-5968
Relation: https://doaj.org/toc/2056-5968
DOI: 10.1038/s41421-024-00668-x
URL الوصول: https://doaj.org/article/7d5757ae6e654746b24b061de00ba934
رقم الأكسشن: edsdoj.7d5757ae6e654746b24b061de00ba934
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20565968
DOI:10.1038/s41421-024-00668-x