Arpc1b, a centrosomal protein, is both an activator and substrate of Aurora A

Molli, Poonam R.; Li, Da Qiang; Bagheri‐Yarmand, Rozita; Pakala, Suresh B.; Katayama, Hiroshi; Sen, Subrata; Iyer, Jyoti; Chernoff, Jonathan; Tsai, Ming Ying; Nair, Sujit S.; Kumar, Rakesh

doi:10.1083/jcb.200908050

Cited by 58 publications

(43 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, Bora cooperates with AurA to activate Plk1 -this leads to the activation of CDK1, which, in turn, contributes to centrosome maturation and mitotic entry (Hutterer et al, 2006;Macůrek et al, 2008;Seki et al, 2008b). Finally, Arpc1b is not only an activator but also a substrate of AurA, and depletion of Arpc1b inhibits the activation of AurA at the centrosome, thereby disturbing mitotic entry (Molli et al, 2010). Of note, all these cofactors share a common mechanism, in that they indirectly induce the phosphorylation of AurA at Thr288.…”

Section: Roles Of Aurora a In Centrosome Maturation And Spindle Formamentioning

confidence: 99%

The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle

Wang

Jiang

Zhang

2014

Journal of Cell Science

View full text Add to dashboard Cite

The centrosome acts as the major microtubule-organizing center (MTOC) for cytoskeleton maintenance in interphase and mitotic spindle assembly in vertebrate cells. It duplicates only once per cell cycle in a highly spatiotemporally regulated manner. When the cell undergoes mitosis, the duplicated centrosomes separate to define spindle poles and monitor the assembly of the bipolar mitotic spindle for accurate chromosome separation and the maintenance of genomic stability. However, centrosome abnormalities occur frequently and often lead to monopolar or multipolar spindle formation, which results in chromosome instability and possibly tumorigenesis. A number of studies have begun to dissect the role of mitotic kinases, including NIMA-related kinases (Neks), cyclindependent kinases (CDKs), Polo-like kinases (Plks) and Aurora kinases, in regulating centrosome duplication, separation and maturation and subsequent mitotic spindle assembly during cell cycle progression. In this Commentary, we review the recent research progress on how these mitotic kinases are coordinated to couple the centrosome cycle with the cell cycle, thus ensuring bipolar mitotic spindle fidelity. Understanding this process will help to delineate the relationship between centrosomal abnormalities and spindle defects.

show abstract

Section: Roles Of Aurora a In Centrosome Maturation And Spindle Formamentioning

confidence: 99%

The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle

Wang

Jiang

Zhang

2014

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…23,24 This multifunctionality is thought to depend on the interaction of AurA with distinct partners/cofactors, such as TPX2, Bora, Ajuba, PAK1, Arpc1b and Hef1. 14,[27][28][29][30][31][32][33][34][35] By contrast, AurB appears to function exclusively as a catalytic subunit of the CPC, which also includes the regulatory/ targeting subunits INCENP, Survivin and Borealin/Dasra. 23,[36][37][38] During mitosis, the CPC relocalizes from kinetochores to the central spindle/midbody and participates in spindle formation, chromatin modification, chromosome bi-orientation, sister chromatid cohesion, cytokinesis and spindle checkpoint function.…”

Section: Promiscuity Versus Selectivitymentioning

confidence: 99%

Aurora kinases and spindle assembly: Variations on a common theme?

Joukov

2011

Cell Cycle

View full text Add to dashboard Cite

“…The AurA-TPX2 complex participates in spindle assembly promoted by chromatin/RanGTP but not by centrosomes and in setting a proper spindle length (11,15,16). Although several factors have been implicated in AurA regulation at centrosomes (7,8,(17)(18)(19), the mechanism of AurA recruitment to and activation at these organelles has been unclear. Hence, the existence of a centrosome-specific AurA activator distinct from TPX2 and other known AurA cofactors has been proposed (20).…”

mentioning

confidence: 99%

Centrosomal protein of 192 kDa (Cep192) promotes centrosome-driven spindle assembly by engaging in organelle-specific Aurora A activation

Joukov

Nicolo

Rodriguez

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

102

187

View full text Add to dashboard Cite

Centrosomes are primary microtubule (MT)-organizing centers (MTOCs). During mitosis, they dramatically increase their size and MT-nucleating activity and participate in spindle assembly from spindle poles. These events require the serine/threonine kinase, Aurora A (AurA), and the centrosomal protein of 192 kDa (Cep192)/spindle defective 2 (Spd-2), but the underlying mechanism remains unclear. We have found that Cep192, unlike targeting protein for Xklp2 (TPX2), a known MT-localizing AurA activator, is an AurA cofactor in centrosome-driven spindle assembly. Cep192, through a direct interaction, targets AurA to mitotic centrosomes where the locally accumulating AurA forms homodimers or oligomers. The dimerization of endogenous AurA, in the presence of bound Cep192, triggers potent kinase activation that, in turn, drives MT assembly. Depletion of Cep192 or specific interference with AurA-Cep192 binding did not prevent AurA oligomerization on MTs but abrogated AurA recruitment to centrosomes and its activation by either sperm nuclei or anti-AurA antibody (αAurA)-induced dimerization. In these settings, MT assembly by both centrosomes and αAurA-coated beads was also abolished or severely compromised. Hence, Cep192 activates AurA by a mechanism different from that previously described for TPX2. The Cep192-mediated mechanism maximizes AurA activity at centrosomes and appears essential for the function of these organelles as MTOCs.

show abstract

Arpc1b, a centrosomal protein, is both an activator and substrate of Aurora A

Abstract: In addition to its function as an Arp2/3 complex subunit, Arp1cb interacts with and stimulates Aurora A at centrosomes, functioning in cell cycle progression.

Cited by 58 publications

References 44 publications

The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle

The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle

Aurora kinases and spindle assembly: Variations on a common theme?

Centrosomal protein of 192 kDa (Cep192) promotes centrosome-driven spindle assembly by engaging in organelle-specific Aurora A activation

Contact Info

Product

Resources

About