BAP31 is involved in T cell activation through TCR signal pathways

Abstract

BAP31 is a ubiquitously expressed endoplasmic reticulum (ER) membrane protein. The functions of BAP31 in the immune system have not been investigated due to the lack of animal models. Therefore we created a BAP31 conditional knockdown mouse by performing a knockdown of BAP31 in the thymus. In doing so, we demonstrate that the maturation of T cells is normal but the number of T cells is less in the thymus of the knockout mouse. In addition, the spleen and lymph nodes of peripheral immune organs contained a lesser proportion of the mature T cells in the thymus specific BAP31 knockout mice. The BAP31 knockout T cells decreased the proliferation activated by TCR signal pathways. Further studies clarified that BAP31 affects the phosphorylation levels of both Zap70/Lck/Lat of the upstream members and Akt/GSK/Jnk/Erk of the downstream members of TCR signal pathways. Furthermore, BAP31 can regulate the expression of some markers such as CD3/TCRα/TCRβ and some cytokines like IL-2/IFN-γ/IL-6/TNF-α which are important for T cell activation. Taken together, these results demonstrate that BAP31 may play an important role in T cell activation by regulating TCR signaling.

A BAP31 intrabody induces gastric cancer cell death by inhibiting p27kip1 proteasome degradation

“…Our previous study reported that BAP31 associates with the N terminus of the CFTRΔF508 and promotes its retro‐translocation from the ER and its degradation by the cytoplasmic 26S proteasome system . In addition, our recent studies clarified that BAP31 is also involved in T cell activation, hepatic lipid accumulation and insulin resistance …”

BAP31 deficiency contributes to the formation of amyloid‐β plaques in Alzheimer's disease by reducing the stability of RTN3

“…Details on the targeting construct and targeting procedure were reported in our previous study (14, 15). Mice with the BAP31 flox allele (BAP31 flox/− ) on the C57BL/6 background were mated with the transgenic mice expressing Cre recombinase under the control of calcium/calmodulin‐dependent protein kinase type II α chain promoter (Camk2a‐Cre mice) to obtain hemizygous Camk2a‐Cre‐BAP31 flox/− offspring.…”

“…Our previous study reported that BAP31 interacted with Sec61 translocons and promoted the retrotranslocation of the CFTR mutant CFTRDF508 to its proteasome degradation pathway (13). Furthermore, our group reported that BAP31 is involved in T cell activation (14), hepatic lipid accumulation, and insulin resistance (15). BAP31 itself is a preferred substrate of caspase‐8, and its cleavage contributes directly to apoptosis progression.…”

B-Cell Receptor-Associated Protein 31 Regulates the Expression of Valosin-Containing Protein Through Elf2

“…S4A). It has been shown that CFTR∆F508 that escapes from degradation by the ERAD pathway can reach the cell membrane [4], therefore, we assessed CFTR∆F508 expression on the cell surface. The results of the flow cytometry analysis showed that more CFTR∆F508 reached the cell surface after 2 hrs of treatment with DBeQ (2.5 μM) (Fig.…”

“…For the Western blot analysis of protein expression, the cells were resuspended in RIPA buffer [4] at 4 °C for 30 min and then centrifuged at 12, 000 rpm for 15 min. Then, 5× sodium dodecyl sulfate (SDS) sample buffer was added to the supernatant, and the sample was boiled.…”