Identification of the auto-inhibitory domains of Aurora-A kinase.
Aurora-A is a centrosome-localized serine/threonine kinase that is overexpressed in multiple human cancers. Here, we report an intramolecular inhibitory regulation in Aurora-A between its N-terminal regulatory domain (aa 1-128, Nt) and the C-terminal catalytic domain (aa 129-403, Cd). Removal of Nt results in a significant increase in kinase activity. Nt inhibited the activity of the single C-terminal kinase domain, but had little effect on the activity of the full-length of Aurora-A. PP1 is not involved in this regulation, instead, Nt interacts Cd directly in vitro and in vivo. The non-Aurora box (aa 64-128) in the N-terminal negatively regulated the kinase activity of the C-terminal kinase domain by intramolecular interaction with aa 240-300 within the C-terminal.
Zhang
Yue
Y
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.
Ni
Jun
J
Huang
Qiang
Q
Ren
Weihua
W
Yu
Long
L
Zhao
Shouyuan
S
D064127:Aurora Kinases; D001665:Binding Sites; D002460:Cell Line; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases