Ring finger protein 213 regulates B-cell receptor signaling, metabolism, and development in B lymphocytes - PubMed
3 days ago
- #B-cell biology
- #RNF213
- #immune signaling
- RNF213 is identified as a key regulator in B-cell biology, influencing development, signaling, and metabolism.
- Deficiency in Rnf213 leads to impaired B-cell receptor (BCR) signaling and compromised metabolic activity in B lymphocytes.
- RNF213 targets the transcription factor SPIB for proteasomal degradation via K11-linked ubiquitylation.
- Stabilized SPIB in Rnf213-deficient B cells upregulates Pik3c3, increasing PI3P production and recruiting PTEN to early endosomes.
- Excess PI3P results in PIP3 hydrolysis, attenuating AKT-mTOR signaling and affecting B-cell development.
- Genetic deletion of Spib or pharmacological inhibition of PIK3C3 restores AKT-mTOR activation and B-cell development in Rnf213-null mice.
- Rnf213 deficiency impairs both T-independent and T-dependent antibody responses, highlighting its role in humoral immunity.
- The study reveals a ubiquitin-dependent circuit linking interferon signaling to transcriptional and metabolic control in B-cell homeostasis.