biostudies-literatureWhillock ALU.S. Department of Health & Human Services | National Institutes of HealthBLRD VANIEHS NIH HHSNIAID NIH HHSNCI NIH HHSNIGMS NIH HHSCenter for Integrated Healthcare, U.S. Department of Veterans Affairs12884https://www.ebi.ac.uk/biostudies/studies/S-EPMC6733949biostudies-literatureUnknown9(1)TRAF3 is a versatile intracellular adapter protein with multiple context-specific roles. Uniquely in B cells, TRAF3 deficiency enhances survival and increases the risk of transformation, as loss of TRAF3 is observed in several types of B cell cancers. Here, we report a new mechanism for TRAF3 in the restraint of B cell survival. We found that TRAF3 deficiency was associated with induction of the pro-survival kinase Pim2 in mouse primary B cells and human malignant B cell lines. The increase in Pim2 was independent of NF-κB2 activation but was ameliorated with inhibition of STAT3 expression or function. TRAF3 deficiency also led to a Pim2-dependent increase in c-Myc protein levels and was associated with reduced c-Myc ubiquitination. TRAF3-deficient primary B cells were less sensitive to ceScientific reportsTRAF3 regulates the oncogenic proteins Pim2 and c-Myc to restrain survival in normal and malignant B cells.PMC6733949T32 AI07485P30 ES005605P30 CA086862T32 AI007485I01 BX001702T32 GM007337T32 AI007533MR I01 BS001702P50 CA097274P50 CA97274Stunz LLWhillock ALLin WWMambetsariev NBishop GAfalseTRAF3 regulates the oncogenic proteins Pim2 and c-Myc to restrain survival in normal and malignant B cells.TRAF3 is a versatile intracellular adapter protein with multiple context-specific roles. Uniquely in B cells, TRAF3 deficiency enhances survival and increases the risk of transformation, as loss of TRAF3 is observed in several types of B cell cancers. Here, we report a new mechanism for TRAF3 in the restraint of B cell survival. We found that TRAF3 deficiency was associated with induction of the pro-survival kinase Pim2 in mouse primary B cells and human malignant B cell lines. The increase in Pim2 was independent of NF-κB2 activation but was ameliorated with inhibition of STAT3 expression or function. TRAF3 deficiency also led to a Pim2-dependent increase in c-Myc protein levels and was associated with reduced c-Myc ubiquitination. TRAF3-deficient primary B cells were less sensitive to ce2019-01-01T00:00:00Z2019 Sep2025-04-21T23:22:11.701Z2020-05-21T18:59:38ZS-EPMC67339493150148110.1038/s41598-019-49390-9