دورية أكاديمية
The discrete roles of individual FOXO transcription factor family members in B-cell malignancies.
العنوان: | The discrete roles of individual FOXO transcription factor family members in B-cell malignancies. |
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المؤلفون: | Lees J; Paul O'Gorman Leukaemia Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom., Hay J; Paul O'Gorman Leukaemia Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom., Moles MW; Paul O'Gorman Leukaemia Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom., Michie AM; Paul O'Gorman Leukaemia Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom. |
المصدر: | Frontiers in immunology [Front Immunol] 2023 May 18; Vol. 14, pp. 1179101. Date of Electronic Publication: 2023 May 18 (Print Publication: 2023). |
نوع المنشور: | Journal Article; Review; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
مواضيع طبية MeSH: | Forkhead Transcription Factors*/genetics , Forkhead Transcription Factors*/metabolism , Neoplasms*/pathology, Humans ; Gene Expression Regulation ; Signal Transduction ; Cell Differentiation |
مستخلص: | Forkhead box (FOX) class O (FOXO) proteins are a dynamic family of transcription factors composed of four family members: FOXO1, FOXO3, FOXO4 and FOXO6. As context-dependent transcriptional activators and repressors, the FOXO family regulates diverse cellular processes including cell cycle arrest, apoptosis, metabolism, longevity and cell fate determination. A central pathway responsible for negative regulation of FOXO activity is the phosphatidylinositol-3-kinase (PI3K)-AKT signalling pathway, enabling cell survival and proliferation. FOXO family members can be further regulated by distinct kinases, both positively (e.g., JNK, AMPK) and negatively (e.g., ERK-MAPK, CDK2), with additional post-translational modifications further impacting on FOXO activity. Evidence has suggested that FOXOs behave as ' bona fide ' tumour suppressors, through transcriptional programmes regulating several cellular behaviours including cell cycle arrest and apoptosis. However, an alternative paradigm has emerged which indicates that FOXOs operate as mediators of cellular homeostasis and/or resistance in both 'normal' and pathophysiological scenarios. Distinct FOXO family members fulfil discrete roles during normal B cell maturation and function, and it is now clear that FOXOs are aberrantly expressed and mutated in discrete B-cell malignancies. While active FOXO function is generally associated with disease suppression in chronic lymphocytic leukemia for example, FOXO expression is associated with disease progression in diffuse large B cell lymphoma, an observation also seen in other cancers. The opposing functions of the FOXO family drives the debate about the circumstances in which FOXOs favour or hinder disease progression, and whether targeting FOXO-mediated processes would be effective in the treatment of B-cell malignancies. Here, we discuss the disparate roles of FOXO family members in B lineage cells, the regulatory events that influence FOXO function focusing mainly on post-translational modifications, and consider the potential for future development of therapies that target FOXO activity. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Lees, Hay, Moles and Michie.) |
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معلومات مُعتمدة: | MR/X008169/1 United Kingdom MRC_ Medical Research Council |
فهرسة مساهمة: | Keywords: B cell malignancy; BCR signalling; FOXO transcription factor; PI3K/AKT; leukemia; lymphoma; tumor suppressor |
المشرفين على المادة: | 0 (Forkhead Transcription Factors) 0 (FOXO6 protein, human) |
تواريخ الأحداث: | Date Created: 20230605 Date Completed: 20230607 Latest Revision: 20240306 |
رمز التحديث: | 20240306 |
مُعرف محوري في PubMed: | PMC10233034 |
DOI: | 10.3389/fimmu.2023.1179101 |
PMID: | 37275916 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1664-3224 |
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DOI: | 10.3389/fimmu.2023.1179101 |