Article
Oncology
Atsushi Tanaka, Koutarou Nishimura, Wataru Saika, Ayana Kon, Yui Koike, Hiromi Tatsumi, June Takeda, Masaki Nomura, Weijia Zang, Manabu Nakayama, Masashi Matsuda, Hiromi Yamazaki, Miki Fukumoto, Hiromi Ito, Yasutaka Hayashi, Toshio Kitamura, Hiroshi Kawamoto, Akifumi Takaori-Kondo, Haruhiko Koseki, Seishi Ogawa, Daichi Inoue
Summary: SETBP1 is a potential epigenetic regulator involved in myeloid malignancies with poor prognosis. Although mutations in SETBP1 are recurrently detected in these malignancies, its role in normal hematopoiesis is poorly understood. This study found that depletion of SETBP1 in normal hematopoiesis had minimal effects on cell functions, suggesting its dispensable role in normal development. Unexpectedly, despite its association with poor outcomes in AML, SETBP1 was found to be dispensable for the development or maintenance of AML. This highlights the concept that a nonessential gene can act as an oncogene when the protein degradation machinery is damaged.
Article
Endocrinology & Metabolism
Jie Zhang, Peilang Yang, Dan Liu, Min Gao, Jizhuang Wang, Xiqiao Wang, Yan Liu, Xiong Zhang
Summary: Dysfunction in keratinocyte differentiation in diabetic skin is closely related to the overexpression of c-Myc and S100A6, with potential mechanisms including activation of the WNT/beta-catenin pathway and direct regulation of S100A6 expression. These findings suggest that c-Myc and S100A6 may be potential targets for the treatment of chronic diabetic wounds.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Genetics & Heredity
Juliana Cazarin, Rachel E. Derollo, Siti Noor Ain Binti Ahmad Shahidan, Jamison B. Burchett, Daniel Mwangi, Saikumari Krishnaiah, Annie L. Hsieh, Zandra E. Walton, Rebekah Brooks, Stephano S. Mello, Aalim M. Weljie, Chi V. Dang, Brian J. Altman
Summary: MYC disrupts the molecular circadian clock, releasing metabolic and biosynthetic processes from circadian control, which may provide an advantage to cancer cells.
Review
Oncology
Xin Wan, Wei Guo, Zhumei Zhan, Ou Bai
Summary: This review focuses on the functions, substrates, and expression of FBW7 in malignant lymphoproliferative disorders. FBW7, as a key component of UPS proteins and a critical tumor suppressor, plays an important role in controlling protein degradation and the development of various cancers.
FRONTIERS IN ONCOLOGY
(2022)
Review
Cell Biology
Wei Fan, Xiaoling Li
Summary: SIRT1 is a crucial NAD(+)-dependent protein deacetylase in mammals, involved in the metabolic and epigenetic regulation of stem cells through deacetylation of transcriptional factors and co-factors. It forms a positive feedback loop with c-Myc, which is important in tumorigenesis. Recent research has uncovered the significance of the SIRT1-c-Myc axis in the regulation of maintenance and differentiation of various stem cells. This review highlights the recent advances in understanding the role of the SIRT1-c-Myc axis in stem cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Liyuan Wang, Chan Chen, Zemin Song, Honghong Wang, Minghui Ye, Donghai Wang, Wenqian Kang, Hudan Liu, Guoliang Qing
Summary: This study demonstrates that EZH2 directly interacts with MYC and MYCN, promoting their stabilization in a methyltransferase-independent manner. By competing against SCFFBW7 ubiquitin ligase, EZH2 counteracts the degradation of MYC and MYCN, highlighting their role as global oncogenic effectors of EZH2. This research suggests that pharmacologic degradation of EZH2 may be a potential therapeutic approach for MYC-driven cancers.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Amalie C. Grenov, Lihee Moss, Sarit Edelheit, Ross Cordiner, Dominik Schmiedel, Adi Biram, Jacob H. Hanna, Torben Heick Jensen, Schraga Schwartz, Ziv Shulman
Summary: This study demonstrates the importance of METTL3 in m(6)A modification, showing that it regulates GC maintenance through the differential functions of m(6)A readers. The findings reveal how m(6)A modulates two independent gene networks supporting critical GC functions through distinct mRNA binders.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Review
Oncology
Anna Borgenvik, Matko Cancer, Sonja Hutter, Fredrik J. Swartling
Summary: MYC genes are frequently misregulated in malignant brain tumors, with MYCN playing a crucial role in pediatric brain tumors. Targeting MYCN for treatment remains challenging due to its nature as a transcription factor. Efforts to treat MYCN-driven brain tumors through direct or indirect measures could potentially improve patient outcomes.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Shanwei Wang, Yanli Wang, Sheng Li, Shen Nian, Wenjing Xu, Fenli Liang
Summary: This study found that the combination of FUBP1 and c-Myc is involved in the progression of colon cancer, and it has clinical significance for understanding the key role of FUBP1 in tumor genesis.
Article
Cell Biology
Xichen Wan, Songjiao Zhao, Yiqin Dai, Jing Zhang, Yan Shen, Lan Gong, Qihua Le
Summary: Our study demonstrated that WNT16b enhances the proliferation and maintains the stemness of hLESCs through the activation of the non-canonical calcium/calcineurin A/NFATC2 pathway in vitro and in vivo. WNT16b binds with Frizzled7, promotes the release of Ca2+, and activates calcineurin A and NFATC2, leading to the increased expression of H3K4me3, H3K14ac, and H3K27ac in the promoter regions of FoxM1 and c-MYC. This study also showed that WNT16b-co-incubated hLESCs can reconstruct a stable ocular surface and inhibit corneal neovascularization in mice with LSCD.
CELL PROLIFERATION
(2023)
Article
Biotechnology & Applied Microbiology
Paivi Pihlajamaa, Otto Kauko, Biswajyoti Sahu, Teemu Kivioja, Jussi Taipale
Summary: This study describes a competitive genome editing method that measures the impact of mutations on molecular functions. By using precision CRISPR editing and template libraries, researchers were able to directly compare the effects between original and mutated cells. The example of the MYC oncogene revealed that E-box mutations at MYC target gene promoters can reduce cellular fitness.
NATURE BIOTECHNOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Aleksandra Boikova, Megan J. Bywater, Gregory A. Quaife-Ryan, Jasmin Straube, Lucy Thompson, Camilla Ascanelli, Trevor D. Littlewood, Gerard I. Evan, James E. Hudson, Catherine H. Wilson
Summary: The study reveals that Myc and HRas can cooperate to induce proliferation in adult mammalian cardiomyocytes, but the activity of HRas also leads to cell death, limiting its potential as a regenerative therapeutic target.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Multidisciplinary Sciences
Kana Tominaga, Naoomi Tominaga, Eric O. Williams, Laura Rufibach, Verena Schowel, Simone Spuler, Mohan Viswanathan, Leonard P. Guarente
Summary: In this study, a cell-based assay was developed to quantitatively assess the membrane localization of DYSF proteins with missense mutations, and 64 localization-defective DYSF mutations were identified. The clinically approved drug 4-PBA was found to partially restore membrane localization to certain mutations and promote membrane repair in cultured myotubes. Oral administration of 4-PBA to mice homozygous for one of these mutations also restored myofiber membrane repair. These findings suggest that 4-PBA may hold therapeutic potential for treating a subset of muscular dystrophy patients with dysferlin deficiency.
Article
Immunology
Michelle S. J. Lee, Takeshi Inoue, Wataru Ise, Julia Matsuo-Dapaah, James B. Wing, Burcu Temizoz, Kouji Kobiyama, Tomoya Hayashi, Ashwini Patil, Shimon Sakaguchi, A. Katharina Simon, Jelena S. Bezbradica, Satoru Nagatoishi, Kouhei Tsumoto, Jun-Ichiro Inoue, Shizuo Akira, Tomohiro Kurosaki, Ken J. Ishii, Cevayir Coban
Summary: This study reveals an unexpected role of TBK1 in germinal center (GC) formation, where it regulates B cell fate by modulating IRF4/BCL6 expression balance and influencing long-term humoral immunity; TBK1-deficient B cells fail to form GC, resulting in memory B cells unable to confer full immunity upon reinfection.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Oncology
Leigh A. Bumpous, Kylie C. Moe, Jing Wang, Logan A. Carver, Alexandria G. Williams, Alexander S. Romer, Jesse D. Scobee, Jack N. Maxwell, Cheyenne A. Jones, Dai H. Chung, William P. Tansey, Qi Liu, April M. Weissmiller
Summary: The MYC family of oncoprotein transcription factors is overexpressed in over 50% of malignancies. The chromatin regulator WDR5 acts as a cofactor for MYC proteins and facilitates their recruitment to chromatin. This study focuses on N-MYC amplified neuroblastoma and demonstrates that WDR5 can facilitate the recruitment of N-MYC to genes associated with protein synthesis and other biological processes. The findings reveal WDR5 as a universal MYC recruiter and highlight the potential coregulation of novel biological functions by N-MYC and WDR5 in sustaining neuroblastoma.
