The diagram is divided into two sections: Physiological Condition on the left and UBE2F Deficiency on the right. In the Physiological Condition section, IL-15 binds to IL-15R, leading to normal expression of IL2rb. JUNB is degraded by CUL5 and UBE2F. In the UBE2F Deficiency section, IL-15 signaling is enhanced. IL2rb is highly expressed, and JUNB is not degraded due to the absence of UBE2F. This leads to the phosphorylation of STAT3 and STAT5, which upregulates Bcl-2 expression.
UBE2F deficiency enhances TM cell survival. Left: In wild-type CD8 TM cells, UBE2F promotes neddylation of CUL5, which activates the CRL5 ubiquitin ligase, leading to JUNB ubiquitination (Ub) and degradation in the proteasome. This regulation restrains IL2b gene expression and IL-15R signaling, thereby limiting the lifespan of CD8 TCM and TPEX cells under physiological conditions. Right: However, in UBE2F-deficient CD8 TM cells, the lack of CUL5 neddylation impairs JUNB ubiquitination and degradation, leading to the accumulation of JUNB. Increased JUNB drives higher IL2rb expression, which enhances IL-15R signaling and consequently promotes the survival of CD8 TCM and TPEX cells, because stronger IL-15R signaling induces greater Bcl-2 gene expression under physiological conditions.