التفاصيل البيبلوغرافية
| العنوان: |
Overexpression of Aurora-A bypasses cytokinesis through phosphorylation of suppressed in lung cancer. |
| المؤلفون: |
Shao-Chih Chiu, Kun-Chieh Chen, Jiun-Yi Hsia, Cheng-Yen Chuang, Chang-Xin Wan, Tong-You Wade Wei, Yun-Ru Jaoying Huang, Jo-Mei Maureen Chen, Yu-Ting Amber Liao, Chang-Tze Ricky Yu |
| المصدر: |
American Journal of Physiology: Cell Physiology; Sep2019, Vol. 317 Issue 3, pC600-C612, 13p |
| مستخلص: |
Mitosis is a complicated process by which eukaryotic cells segregate duplicated genomes into two daughter cells. To achieve the goal, numerous regulators have been revealed to control mitosis. The oncogenic Aurora-A is a versatile kinase responsible for the regulation of mitosis including chromosome condensation, spindle assembly, and centrosome maturation through phosphorylating a range of substrates. However, overexpression of Aurora-A bypasses cytokinesis, thereby generating multiple nuclei by unknown the mechanisms. To explore the underlying mechanisms, we found that SLAN, a potential tumor suppressor, served as a substrate of Aurora-A and knockdown of SLAN induced immature cytokinesis. Aurora-A phosphorylates SLAN at T573 under the help of the scaffold protein 14-3-3η. The SLAN phosphorylation-mimicking mutants T573D or T573E, in contrast to the phosphorylation-deficiency mutant T573A, induced higher level of multinucleated cells, and the endogenous SLAN p573 resided at spindle midzone and midbody with the help of the microtubule motor MKLP1. The Aurora-A- or SLAN-induced multiple nuclei was prevented by the knockdown of 14-3-3η or Aurora-A respectively, thereby revealing a 14-3-3η/Aurora-A/SLAN cascade negatively controlling cytokinesis. Intriguingly, SLAN T573D or T573E inactivated and T573A activated the key cytokinesis regulator RhoA. RhoA interacted with SLAN np573, i.e., the nonphosphorylated form of SLAN at T573, which localized to the spindle midzone dictated by RhoA and ECT2. Therefore, we report here that SLAN mediates the Aurora-A-triggered cytokinesis bypass and SLAN plays dual roles in that process depending on its phosphorylation status. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
