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Differential roles of RUBCN isoforms in autophagy and memory B-cell generation

ABSTRACT: RUBCN/Rubicon was originally identified as a negative regulator of canonical autophagy. However, its function remains controversial. Here we show that RUBCN is expressed as two isoforms of different sizes, RUBCN130 and RUBCN100, that are translated from alternative translation initiation sites. Selective RUBCN130 deficiency in B cells enhances autophagy and memory B-cell generation. Autophagy suppression by ATG7 deficiency reverses the enhancement of memory B-cell generation in B-cell–specific RUBCN130-deficient mice. While RUBCN130 is intracellularly localized in late endosomes and lysosomes, RUBCN100 is preferentially located in early endosomes and enhances the enzymatic activity of class III PI(3)K VPS34. Additionally, RUBCN100 plays a positive regulatory role in autophagy since its expression promotes autophagy and suppresses mTORC1 activation. Our findings reveal the critical role of functional interaction between RUBCN isoforms in autophagy regulation and also provide clues for developing a new vaccine strategy to induce efficient B-cell memory.

ORGANISM(S): Mus musculus

PROVIDER: GSE202133 | GEO | 2023/09/19

REPOSITORIES: GEO

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