Disease relevance of Aurka

• Overexpression of Aurora-A readily transforms rat-1 and NIH3T3 cells, but not primary cells, whereas overexpression of Aurora-B induces metastasis after implantation of tumors in nude mice [1].
• In clinical samples, levels of Aurora-A and Aurora-B were significantly elevated in prostatic intraepithelial neoplasia lesions and prostate tumors when compared with the non-neoplastic samples [2].
• Here, we report that Aurora-A and Aurora-B are highly expressed in primary human and mouse prostate cancers and prostate cancer cell lines [2].
• Cre-loxP-controlled periodic Aurora-A overexpression induces mitotic abnormalities and hyperplasia in mammary glands of mouse models [3].
• Consistent with these observations, acute loss of Aurora-A by small interfering RNA resulted in reduced phosphorylation of BRCA1 Ser(308), and transient infection of adenovirus Aurora-A increased Ser(308) phosphorylation [4].
• Expression of E2F3 positively correlates with the protein level of Aurora-A in human ovarian cancer examined [5].

High impact information on Aurka

• Chfr deficiency leads to chromosomal instability in embryonic fibroblasts and regulates the mitotic kinase Aurora A, which is frequently upregulated in a variety of tumors [6].
• Collectively, our data suggest that Chfr is a tumor suppressor and ensures chromosomal stability by controlling the expression levels of key mitotic proteins such as Aurora A [6].
• Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit [7].
• The mitotic kinase Aurora A (Aur-A) is required for formation of a bipolar mitotic spindle and accurate chromosome segregation [7].
• PAK1 promotes phosphorylation of Aurora-A on Thr288 and Ser342, which are key sites for kinase activation in mitosis [8].

Chemical compound and disease context of Aurka

• Treatment of animals carrying tumor IAK 109D with 3,5,3'-triiodo-L-thyronine (T3) (5 micrograms/100 g body weight) for 2 hr reduced TSH-beta gene transcription to less than 10% of control levels, whereas alpha RNA synthesis was reduced to 59% of control [9].

Biological context of Aurka

• These results indicate that transgenic Aurora A is protected from degradation within G(2)-M but is immediately degraded after translation in the G(1)-S stage of the cell cycle [10].
• The conditional expression of Aurora-A resulted in significantly increased binucleated cell formation and apoptosis in the mammary epithelium [3].
• Induction of Aurora-A overexpression in mouse embryonic fibroblasts prepared from the transgenic mice also led to aberrant mitosis and binucleated cell formation followed by apoptosis [3].
• Caenorhabditis elegans Aurora A kinase AIR-1 is required for postembryonic cell divisions and germline development [11].
• During early embryo development, aurora-A was found in association with the mitotic spindle poles [12].

Anatomical context of Aurka

• Under the exponential growth conditions of MEF cells, transgenic Aurora A was detected within the mitotic stage of the cell cycle and localized to centrosomes [10].
• Cell lines and primary tumors derived from the TRAMP model were also found to express high levels of Aurora-A and Aurora-B [2].
• Interestingly, expression of Aurora-A in non-neoplastic prostates correlated with seminal vesicle invasion (rho = 0.275, P = 0.0169) and in prostate tumor with positive surgical margins (rho = 0.265, P = 0.0161) [2].
• Here, we created a transgenic mouse model to investigate the involvement of Aurora-A overexpression in the development of mammary glands and tumorigenesis using a Cre-loxP system [3].
• The quantity of aurora-A protein was high in the germinal vesicle (GV) and metaphase II (MII) oocytes and remained stable during other meiotic maturation stages [12].

Associations of Aurka with chemical compounds

• These proteins promote polyadenylation and translation by stimulating Aurora A catalyzed CPEB serine 174 phosphorylation [13].
• Two coding single nucleotide polymorphisms in Aurora-A, 91T>A [phenylalanine/isoleucine (F/I)] and 169G>A [valine/isoleucine (V/I)], create four haplotypes, 91T-169G, 91A-169G, 91T-169A, and 91A-169A [14].
• STK15/Aurora-A is a serine/threonine kinase essential for chromosome segregation and cytokinesis, and is considered to be a cancer susceptibility gene in mice and humans [14].
• Finally, we present evidence suggesting that TRAP/Mediator is recruited to the Aurora-A gene via direct interactions between TRAP220/MED1 and the Ets-related transcription factor GABP [15].
• Our results demonstrate that quinazolines with a substituted aminothiazole at C4 possess potent Aurora A and B inhibitory activity and excellent selectivity against a panel of various serine-threonine and tyrosine kinases, as exemplified by compound 46 [16].

Other interactions of Aurka

• The central kinase domain of AIE1 revealed 77.6% and 66.3% identity with that of STK-1 and IAK1/Ayk1, but much less homology was found in the sequence outside the kinase domain [17].
• In vitro studies using mouse embryo fibroblasts demonstrate that inhibition of Aurora-A can have either positive or negative effects on cell growth as a function of p53 status [18].

Analytical, diagnostic and therapeutic context of Aurka

• Although transcripts for Aurora A were elevated in multiple organs of the transgenic mice, the corresponding protein was not detected in extracts analyzed by immunoblotting [10].
• The subcellular localization of aurora-A during oocyte meiotic maturation, fertilization, and early cleavages as well as after antibody microinjection or microtubule assembly perturbance was studied with confocal microscopy [12].
• Frequent overexpression of STK15/Aurora-A/BTAK and chromosomal instability in tumorigenic cell cultures derived from human ovarian cancer [19].
• Among the down-regulated genes revealed by cDNA microarray analyses, we identified Aurora-A, a centrosome kinase that plays a critical role in regulating M phase events and is frequently amplified in several types of cancer [15].
• Furthermore, chromatin immunoprecipitation assays show that TRAP220/MED1-containing TRAP/Mediator complexes directly bind to the Aurora-A promoter in vivo [15].

References