Limits...
Aurora Kinases and Potential Medical Applications of Aurora Kinase Inhibitors: A Review.

Gavriilidis P, Giakoustidis A, Giakoustidis D - J Clin Med Res (2015)

Bottom Line: Any inactivation of them can have catastrophic consequences on mitotic events of spindle formation, alignment of centrosomes and cytokinesis, resulting in apoptosis.Overexpression of AKs has been detected in diverse solid and hematological cancers and has been linked with a dismal prognosis.After discovery and identification of the first aurora kinase inhibitor (AKI) ZM447439 as a potential drug for targeted therapy in cancer treatment, approximately 30 AKIs have been introduced in cancer treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Oncology, Theageneio Anticancer Hospital, Thessaloniki, Greece.

ABSTRACT
Aurora kinases (AKs) represent a novel group of serine/threonine kinases. They were originally described in 1995 by David Glover in the course of studies of mutant alleles characterized with unusual spindle pole configuration in Drosophila melanogaster. Thus far, three AKs A, B, and C have been discovered in human healthy and neoplastic cells. Each one locates in different subcellular locations and they are all nuclear proteins. AKs are playing an essential role in mitotic events such as monitoring of the mitotic checkpoint, creation of bipolar mitotic spindle and alignment of centrosomes on it, also regulating centrosome separation, bio-orientation of chromosomes and cytokinesis. Any inactivation of them can have catastrophic consequences on mitotic events of spindle formation, alignment of centrosomes and cytokinesis, resulting in apoptosis. Overexpression of AKs has been detected in diverse solid and hematological cancers and has been linked with a dismal prognosis. After discovery and identification of the first aurora kinase inhibitor (AKI) ZM447439 as a potential drug for targeted therapy in cancer treatment, approximately 30 AKIs have been introduced in cancer treatment.

No MeSH data available.


Related in: MedlinePlus

AKs contain mainly two domains: 1) NH2-terminal regulatory domain (white), 2) COOH-terminal catalytic domain (yellow). The three auroras A, B, and C share great homology in the catalytic domain. Phosphorylation at threonine within the activation loop is necessary for kinase activity.
© Copyright Policy - open access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4554212&req=5

Figure 1: AKs contain mainly two domains: 1) NH2-terminal regulatory domain (white), 2) COOH-terminal catalytic domain (yellow). The three auroras A, B, and C share great homology in the catalytic domain. Phosphorylation at threonine within the activation loop is necessary for kinase activity.

Mentions: The first human homologue of AKs was described by Bischoff and Zhou in 1998 [4, 8]. So far in human cells, three AKs were identified: A, B and C [9]. AKs structure has been conserved during eukaryotic evolution [1]. They comprise two domains: the NH2-terminal regulatory domain and the COOH-terminal catalytic domain. All three share great homology in the catalytic domain but differ in the regulatory [10, 11] (Fig. 1). In 2004, the first patient was treated with aurora kinase inhibitor (AKI) (PHA-739358) [12]. The translational period was only 8 years. Comparing with the translational period of other targeted therapies, we can remark a real progress.


Aurora Kinases and Potential Medical Applications of Aurora Kinase Inhibitors: A Review.

Gavriilidis P, Giakoustidis A, Giakoustidis D - J Clin Med Res (2015)

AKs contain mainly two domains: 1) NH2-terminal regulatory domain (white), 2) COOH-terminal catalytic domain (yellow). The three auroras A, B, and C share great homology in the catalytic domain. Phosphorylation at threonine within the activation loop is necessary for kinase activity.
© Copyright Policy - open access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554212&req=5

Figure 1: AKs contain mainly two domains: 1) NH2-terminal regulatory domain (white), 2) COOH-terminal catalytic domain (yellow). The three auroras A, B, and C share great homology in the catalytic domain. Phosphorylation at threonine within the activation loop is necessary for kinase activity.
Mentions: The first human homologue of AKs was described by Bischoff and Zhou in 1998 [4, 8]. So far in human cells, three AKs were identified: A, B and C [9]. AKs structure has been conserved during eukaryotic evolution [1]. They comprise two domains: the NH2-terminal regulatory domain and the COOH-terminal catalytic domain. All three share great homology in the catalytic domain but differ in the regulatory [10, 11] (Fig. 1). In 2004, the first patient was treated with aurora kinase inhibitor (AKI) (PHA-739358) [12]. The translational period was only 8 years. Comparing with the translational period of other targeted therapies, we can remark a real progress.

Bottom Line: Any inactivation of them can have catastrophic consequences on mitotic events of spindle formation, alignment of centrosomes and cytokinesis, resulting in apoptosis.Overexpression of AKs has been detected in diverse solid and hematological cancers and has been linked with a dismal prognosis.After discovery and identification of the first aurora kinase inhibitor (AKI) ZM447439 as a potential drug for targeted therapy in cancer treatment, approximately 30 AKIs have been introduced in cancer treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Oncology, Theageneio Anticancer Hospital, Thessaloniki, Greece.

ABSTRACT
Aurora kinases (AKs) represent a novel group of serine/threonine kinases. They were originally described in 1995 by David Glover in the course of studies of mutant alleles characterized with unusual spindle pole configuration in Drosophila melanogaster. Thus far, three AKs A, B, and C have been discovered in human healthy and neoplastic cells. Each one locates in different subcellular locations and they are all nuclear proteins. AKs are playing an essential role in mitotic events such as monitoring of the mitotic checkpoint, creation of bipolar mitotic spindle and alignment of centrosomes on it, also regulating centrosome separation, bio-orientation of chromosomes and cytokinesis. Any inactivation of them can have catastrophic consequences on mitotic events of spindle formation, alignment of centrosomes and cytokinesis, resulting in apoptosis. Overexpression of AKs has been detected in diverse solid and hematological cancers and has been linked with a dismal prognosis. After discovery and identification of the first aurora kinase inhibitor (AKI) ZM447439 as a potential drug for targeted therapy in cancer treatment, approximately 30 AKIs have been introduced in cancer treatment.

No MeSH data available.


Related in: MedlinePlus