کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8470614 | 1550009 | 2015 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The Aspergillus nidulans bimC4 mutation provides an excellent tool for identification of kinesin-14 inhibitors
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: The Aspergillus nidulans bimC4 mutation provides an excellent tool for identification of kinesin-14 inhibitors The Aspergillus nidulans bimC4 mutation provides an excellent tool for identification of kinesin-14 inhibitors](/preview/png/8470614.png)
چکیده انگلیسی
Centrosome amplification is a hallmark of many types of cancer cells, and clustering of multiple centrosomes is critical for cancer cell survival and proliferation. Human kinesin-14 HSET/KFIC1 is essential for centrosome clustering, and its inhibition leads to the specific killing of cancer cells with extra centrosomes. Since kinesin-14 motor domains are conserved evolutionarily, we conceived a strategy of obtaining kinesin-14 inhibitors using Aspergillus nidulans, based on the previous result that loss of the kinesin-14 KlpA rescues the non-viability of the bimC4 kinesin-5 mutant at 42 °C. However, it was unclear whether alteration of BimC or any other non-KlpA protein would be a major factor reversing the lethality of the bimC4 mutant. Here we performed a genome-wide screen for bimC4 suppressors and obtained fifteen suppressor strains. None of the suppressor mutations maps to bimC. The vast majority of them contain mutations in the klpA gene, most of which are missense mutations affecting the C-terminal motor domain. Our study confirms that the bimC4 mutant is suitable for a cell-based screen for chemical inhibitors of kinesin-14. Since the selection is based on enhanced growth rather than diminished growth, cytotoxic compounds can be excluded.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Fungal Genetics and Biology - Volume 82, September 2015, Pages 51-55
Journal: Fungal Genetics and Biology - Volume 82, September 2015, Pages 51-55
نویسندگان
Betsy Wang, Kristin Li, Max Jin, Rongde Qiu, Bo Liu, Berl R. Oakley, Xin Xiang,