S-Space College of Medicine/School of Medicine (의과대학/대학원) Pathology (병리학전공) Journal Papers (저널논문_병리학전공)
Negative feedback regulation of Aurora-A via phosphorylation of Fas-associated factor-1
- Issue Date
- J Biol Chem. 283(47), 32344-32351
- Adaptor Proteins, Signal Transducing/*metabolism ; Animals ; Carrier Proteins/*metabolism ; Cell Cycle ; Feedback, Biochemical ; Hela Cells ; Humans ; Mice ; Mice, Inbred BALB C ; Phosphorylation ; Proteasome Endopeptidase Complex/metabolism ; Protein-Serine-Threonine Kinases/*biosynthesis/physiology ; RNA Interference ; Gene Expression Regulation, Enzymologic
- This study reports that Aurora-A (Aur-A) phosphorylates Fas-associated factor-1 (FAF1) at Ser-289 and Ser-291. Forced expression of a FAF1 mutant mimicking phosphorylation at Ser-289 and Ser-291 (FAF1 DD), but not phosphorylation-deficient FAF1 (FAF1 AA), reduced Aur-A expression. However, transfection of FAF1 DD failed to reduce Aur-A expression in the presence of MG132 and MG115, indicating that this decrease is proteasome-mediated. Additionally, transfection of FAF1 DD suppressed the expression of Aur-A in ts20-BALB cells lacking E1 ubiquitin (Ub) activating enzyme activity at restrictive temperatures and also reduced the expression of Aur-A S51D, a mutant resistant to Ub-dependent degradation. Our data indicate that phosphorylated FAF1 mediates the ubiquitin-independent, proteasome-dependent degradation of Aur-A. Overexpression of FAF1 DD blocked Aur-A-induced centrosome amplification and accumulated cells in G(2)/M phase, representing cellular phenotypes consistent with the anticipated loss of Aur-A. Collectively, our findings support the negative feedback regulation of Aur-A via phosphorylation of the death-promoting protein, FAF1, and disclose the presence of molecular cross-talk between constituents of the cell cycle and cell death machinery.
- 0021-9258 (Print)
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