Casein kinase II activates Bik to induce death of hyperplastic mucous cells in a cell cycle‐dependent manner

Abstract

Extensive inflammation causes epithelial cell hyperplasia in the airways and Bcl-2interacting killer (Bik) reduces epithelial cell and mucous cell hyperplasia without affecting resting cells to restore homeostasis. These observations suggest that Bik induces apoptosis in a cell cycle-specific manner, but the mechanisms are not understood. Mice were exposed to an allergen for 3, 14, or 30 days and Bik expression was induced in airway epithelia of transgenic mice. Bik reduced epithelial and mucous cell hyperplasia when mice were exposed to an allergen for 3 or 14 days, but not when exposure lasted for 30 days, and Ki67-positivity was reduced. In culture, Bik expression killed proliferating cells but not quiescent cells. To capture the stage

Bik promotes proteasomal degradation to control low-grade inflammation

“…We have reported that phosphorylation of Bik at T33 and S35 is required for Bik to cause cell death in epithelial cells in a cell cycle–dependent manner ( 44 ). Thus, we explored the role of Bik phosphorylation in facilitating p65 degradation using Bik expression constructs that have either constitutively nonphosphorylated (T33A and S35A) or constitutively phosphorylated (T33D, S35D, and T33/S35DD) mutants.…”