Academic Journal
Opposing roles of RUBCN isoforms in autophagy and memory B cell generation
| العنوان: | Opposing roles of RUBCN isoforms in autophagy and memory B cell generation |
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| المؤلفون: | Tsai, Chao-Yuan, Sakakibara, Shuhei, Kuan, Yu-Diao, Omori, Hiroko, El Hussien, Maruwa Ali, Okuzaki, Daisuke, Lu, Shiou-Ling, Noda, Takeshi, Tabata, Keisuke, Nakamura, Shuhei, Yoshimori, Tamotsu, Kikutani, Hitoshi |
| المصدر: | Science Signaling ; volume 16, issue 803 ; ISSN 1945-0877 1937-9145 |
| بيانات النشر: | American Association for the Advancement of Science (AAAS) |
| سنة النشر: | 2023 |
| الوصف: | RUBCN (also known as Rubicon) was originally identified as a negative regulator of autophagy, a process by which cells degrade and recycle damaged components or organelles and that requires the activity of the class III PI3K VPS34 and the mTORC1 protein complex. Here, we characterized the role of a shorter isoform, RUBCN 100 , as an autophagy-promoting factor in B cells. RUBCN 100 was translated from alternative translation initiation sites and lacked the RUN domain of the longer, previously characterized RUBCN 130 isoform. Specific deficiency of RUBCN 130 in B cells enhanced autophagy, which promoted memory B cell generation. In contrast to RUBCN 130 , which is localized in late endosomes and lysosomes and suppresses the enzymatic activity of VPS34, an effect thought to mediated by its RUN domain, RUBCN 100 was preferentially located in early endosomes and enhanced VPS34 activity, presumably because of the absence of the RUN domain. Furthermore, RUBCN 100 , but not RUBCN 130 , enhanced autophagy and suppressed mTORC1 activation. Our findings reveal that the opposing roles of two RUBCN isoforms are critical for autophagy regulation and memory B cell differentiation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1126/scisignal.ade3599 |
| الاتاحة: | http://dx.doi.org/10.1126/scisignal.ade3599 https://www.science.org/doi/pdf/10.1126/scisignal.ade3599 |
| رقم الانضمام: | edsbas.8FA7CAC5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1126/scisignal.ade3599 |
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