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

被引:31
作者
Loukil, Abdelhalim [1 ]
Zonca, Manuela [1 ]
Rebouissou, Cosette [1 ]
Baldin, Veronique [2 ]
Coux, Olivier [2 ]
Biard-Piechaczyk, Martine [3 ]
Blanchard, Jean-Marie [1 ]
Peter, Marion [1 ]
机构
[1] Univ Montpellier I, Univ Montpellier 2, CNRS, Inst Genet Mol Montpellier, F-34293 Montpellier, France
[2] Univ Montpellier I, Univ Montpellier 2, CNRS, Ctr Rech Biochim Macromol, F-34293 Montpellier, France
[3] Univ Montpellier I, Univ Montpellier 2, CNRS, Ctr Etud Agents Pathogenes & Biotechnol Sante, F-34293 Montpellier, France
关键词
FLIM; FRET; Autophagy; Cyclin A2; Mitosis; Ubiquitin-proteasome system; ANAPHASE-PROMOTING COMPLEX/CYCLOSOME; SPINDLE ASSEMBLY CHECKPOINT; CDC25B PHOSPHATASE; MULTIPHOTON-FLIM; DNA-REPLICATION; M-PHASE; MITOSIS; LOCALIZATION; DESTRUCTION; ACCUMULATION;
D O I
10.1242/jcs.139188
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cyclin A2 is a key player in the regulation of the cell cycle. 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. Forster (or fluorescence) resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy (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 induces the stabilisation of a subset of cyclin A2, whereas induction of autophagy accelerates the degradation of cyclin A2, thus showing that autophagy is a novel regulator of cyclin A2 degradation.
引用
收藏
页码:2145 / 2150
页数:6
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