JunB breakdown in mid-/late G2 is required for down-regulation of cyclin A2 levels and proper mitosis.
JunB, a member of the AP-1 family of dimeric transcription factors, is best known as a cell proliferation inhibitor, a senescence inducer, and a tumor suppressor, although it also has been attributed a cell division-promoting activity. Its effects on the cell cycle have been studied mostly in G1 and S phases, whereas its role in G2 and M phases still is elusive. Using cell synchronization experiments, we show that JunB levels, which are high in S phase, drop during mid- to late G2 phase due to accelerated phosphorylation-dependent degradation by the proteasome. The forced expression of an ectopic JunB protein in late G2 phase indicates that JunB decay is necessary for the subsequent reduction of cyclin A2 levels in prometaphase, the latter event being essential for proper mitosis. Consistently, abnormal JunB expression in late G2 phase entails a variety of mitotic defects. As these aberrations may cause genetic instability, our findings contrast with the acknowledged tumor suppressor activity of JunB and reveal a mechanism by which the deregulation of JunB might contribute to tumorigenesis.
Farràs
Rosa
R
Institut de Génétique Moléculaire de Montpellier, CNRS, 1919 route de Mende, 34293 Montpellier Cedex 05, France. rfarras@cipf.es
Baldin
Véronique
V
Gallach
Sandra
S
Acquaviva
Claire
C
Bossis
Guillaume
G
Jariel-Encontre
Isabelle
I
Piechaczyk
Marc
M
D002453:Cell Cycle; D019925:Cyclin A / Q000378:metabolism*; D056751:Cyclin A2; D015536:Down-Regulation; D016195:G2 Phase; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008954:Models, Biological; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*
C503721:CCNA2 protein, human; D019925:Cyclin A; D056751:Cyclin A2; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D046988:Proteasome Endopeptidase Complex