Arpc1b, a centrosomal protein, is both an activator and substrate of Aurora A.
Here we provide evidence in support of an inherent role for Arpc1b, a component of the Arp2/3 complex, in regulation of mitosis and demonstrate that its depletion inhibits Aurora A activation at the centrosome and impairs the ability of mammalian cells to enter mitosis. We discovered that Arpc1b colocalizes with gamma-tubulin at centrosomes and stimulates Aurora A activity. Aurora A phosphorylates Arpc1b on threonine 21, and expression of Arpc1b but not a nonphosphorylatable Arpc1b mutant in mammalian cells leads to Aurora A kinase activation and abnormal centrosome amplification in a Pak1-independent manner. Together, these findings reveal a new function for Arpc1b in centrosomal homeostasis. Arpc1b is both a physiological activator and substrate of Aurora A kinase and these interactions help to maintain mitotic integrity in mammalian cells.
Molli
Poonam R
PR
Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC 20037, USA.
Li
Da-Qiang
DQ
Bagheri-Yarmand
Rozita
R
Pakala
Suresh B
SB
Katayama
Hiroshi
H
Sen
Subrata
S
Iyer
Jyoti
J
Chernoff
Jonathan
J
Tsai
Ming-Ying
MY
Nair
Sujit S
SS
Kumar
Rakesh
R
D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D064127:Aurora Kinases; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism*; D020536:Enzyme Activators / Q000378:metabolism*; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D009154:Mutation; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
C460821:ARPC1B protein, human; D051376:Actin-Related Protein 2-3 Complex; D020536:Enzyme Activators; D014404:Tubulin; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases