Naf1alpha is phosphorylated in mitotic phase and required to protect cells against apoptosis.

Naf1alpha is an HIV Nef-associated factor expressed ubiquitously in human cells. Previously, we reported that Naf1alpha is phosphorylated with EGF through MEK/ERK2 pathway. In this study, we found an additional phosphorylation of Naf1alpha when cells are in mitotic phase (M phase) or arrested in M phase with anti-mitosis reagents, and disappeared when the cells exit from mitotic phase to G1 phase. Furthermore, we demonstrated that Naf1alpha plays an important role in preventing cells from apoptosis: over-expression of Naf1alpha in Saos-2 cells suppressed trichostatin A (TSA)-induced apoptosis either of random culture or of cell population synchronized in M phase. In addition, knock-down of Naf1alpha expression with small interfering RNA sensitized Saos-2 cells to TSA-induced apoptosis. Physiological significance of these findings is discussed in relation to protection of cells from the apoptosis induction.