GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300099/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300099GEOGSEfalseControl of CD8+ T central memory cell formation via ADAP regulation of TRIM21-mediated ubiquitination of ZEB2The ADAP-SKAP1 signaling module plays a critical role in TCR-mediated activation and LFA-1-dependent adhesion; however, its regulatory function in balancing CD8+ T-cell effector differentiation, memory formation, and exhaustion remains poorly understood. Here, we demonstrated that ADAP deficiency drives CD8+ T-cell polarization toward a central memory phenotype (CD44Hi CD62LHi). During acute lymphocytic choriomeningitis virus (LCMV) Armstrong infection, Adap-/- CD8+ T cells exhibit accelerated effector differentiation, marked by elevated expression of CX3CR1, IFN-γ and granzyme B. Functional analyses revealed that ADAP-deficient CD8+ T cells display heightened cytotoxic capacity in vitro. RNA sequencing (RNA-seq) further identified ZEB2 as the most significantly upregulated transcription factor in Adap-/- CD8+ T cells. Mechanistically, ADAP interacts with the E3 ubiquitin ligase TRIM21 and positively regulates TRIM21-mediated K48-linked polyubiquitination of ZEB2, thereby impairing its binding to the SMAD3 promoter. Collectively, our findings define an ADAP-TRIM21-ZEB2 axis that governs CD8+ T-cell differentiation plasticity, offering novel insights into therapeutic strategies for modulating T-cell responses.2026/05/11GSE300099GSM9053690GSM9053698GSM9053687GSM9053697GSM9053686GSM9053696GSM9053685GSM9053695GSM9053694GSM9053693GSM9053692GSM9053691GSM9053704GSM9053703GSM9053702GSM9053701GSM9053700GSM9053689GSM9053699GSM905368824247300099Mus musculus