# FEM1B enhances TRAIL‐induced apoptosis in T lymphocytes and monocytes

## TL;DR

FEM1B promotes TRAIL-induced cell death in T lymphocytes and monocytes through different mechanisms involving caspase activation and TRAF2 or TRAIL-R2 regulation.

## Contribution

This study reveals novel mechanisms by which FEM1B enhances TRAIL-induced apoptosis in immune cells via distinct pathways in T lymphocytes and monocytes.

## Key findings

- FEM1B knockdown reverses increased apoptosis in transfected cells.
- FEM1B activates caspase-3 and caspase-8 but not caspase-9 in TRAIL-stimulated cells.
- FEM1B interacts with TRAF2 in T lymphocytes and upregulates TRAIL-R2 in monocytes to promote apoptosis.

## Abstract

FEM1B is recognized for its significant pro‐apoptotic function in colorectal cancer; however, its influence and mechanisms regarding apoptosis in immune cells remain inadequately elucidated. In this study, we demonstrated that FEM1B enhances TRAIL‐induced apoptosis in Molt‐4, Jurkat, THP‐1, and U937 cell lines. Notably, the knockdown of FEM1B in transfected cells resulted in a reversal of the observed increase in cell apoptosis. Our findings indicate that FEM1B activates caspase‐3 and caspase‐8, but not caspase‐9, in response to TRAIL stimulation, suggesting its involvement in the extrinsic caspase‐dependent apoptotic pathway. Furthermore, we found that FEM1B interacted with TRAF2 and downregulates its expression in Molt‐4 and Jurkat cells, thereby diminishing TRAF2's inhibitory effect on caspase‐8. In THP‐1 and U937 cells, FEM1B was found to upregulate TRAIL‐R2, thereby promoting TRAIL‐induced apoptosis. Knockout studies in murine models further corroborated that FEM1B facilitates TRAIL‐induced apoptosis. These results demonstrate that FEM1B enhances TRAIL‐induced apoptosis in T lymphocytes and monocytes through a caspase‐dependent mechanism involving TRAF2 or TRAIL receptors.

FEM1B facilitates TRAIL‐induced apoptosis through distinct mechanisms in T lymphocytes and monocytes. In T lymphocytes, FEM1B engages with TRAF2, leading to a reduction in TRAF2 expression, which subsequently lessens TRAF2's inhibitory influence on caspase‐8. Conversely, in monocytes, FEM1B is observed to enhance the expression of TRAIL‐R2, which in turn promotes the activation of caspase‐3, thereby augmenting TRAIL‐induced apoptosis.