title: Arpc1b, a centrosomal protein, is both an activator and substrate of Aurora A.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC 20037, USA.
authors.forename: Poonam R
authors.initials: PR
authors.lastname: Molli
authors.forename: Da-Qiang
authors.initials: DQ
authors.lastname: Li
authors.forename: Rozita
authors.initials: R
authors.lastname: Bagheri-Yarmand
authors.forename: Suresh B
authors.initials: SB
authors.lastname: Pakala
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katayama
authors.forename: Subrata
authors.initials: S
authors.lastname: Sen
authors.forename: Jyoti
authors.initials: J
authors.lastname: Iyer
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chernoff
authors.forename: Ming-Ying
authors.initials: MY
authors.lastname: Tsai
authors.forename: Sujit S
authors.initials: SS
authors.lastname: Nair
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
mesh_terms: 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
chemical_list: C460821:ARPC1B protein, human; D051376:Actin-Related Protein 2-3 Complex; D020536:Enzyme Activators; D014404:Tubulin; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases