High resolution live cell imaging reveals novel cyclin A2 degradation foci involving autophagy

Abstract

Cyclin A2 is a key actor in cell cycle regulation. Its degradation in mid-mitosis relies on the ubiquitin-proteasome system (UPS). Using high resolution microscopic imaging, we find that cyclin A2 persists beyond metaphase. Indeed, we identify a novel cyclin A2-containing compartment that forms dynamic foci. FRET and FLIM analyses show that cyclin A2 ubiquitylation takes place predominantly in these foci before spreading throughout the cell. Moreover, inhibition of autophagy in proliferating cells induce a stabilisation of a cyclin A2 subset, while induction of autophagy accelerates cyclin A2 degradation, thus showing that autophagy is a novel regulator of cyclin A2 degradation.