Meirelles Gabriela Vaz, Perez Arina Marina, de Souza Edmárcia Elisa, Basei Fernanda Luisa, Papa Priscila Ferreira, Melo Hanchuk Talita Diniz, Cardoso Vanessa Bomfim, Kobarg Jörg
Gabriela Vaz Meirelles, Arina Marina Perez, Edmárcia Elisa de Souza, Fernanda Luisa Basei, Priscila Ferreira Papa, Talita Diniz Melo Hanchuk, Vanessa Bomfim Cardoso, Jörg Kobarg, Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP 13084-971, Brazil.
World J Biol Chem. 2014 May 26;5(2):141-60. doi: 10.4331/wjbc.v5.i2.141.
Aside from Polo and Aurora, a third but less studied kinase family involved in mitosis regulation is the never in mitosis-gene A (NIMA)-related kinases (Neks). The founding member of this family is the sole member NIMA of Aspergillus nidulans, which is crucial for the initiation of mitosis in that organism. All 11 human Neks have been functionally assigned to one of the three core functions established for this family in mammals: (1) centrioles/mitosis; (2) primary ciliary function/ciliopathies; and (3) DNA damage response (DDR). Recent findings, especially on Nek 1 and 8, showed however, that several Neks participate in parallel in at least two of these contexts: primary ciliary function and DDR. In the core section of this in-depth review, we report the current detailed functional knowledge on each of the 11 Neks. In the discussion, we return to the cross-connections among Neks and point out how our and other groups' functional and interactomics studies revealed that most Neks interact with protein partners associated with two if not all three of the functional contexts. We then raise the hypothesis that Neks may be the connecting regulatory elements that allow the cell to fine tune and synchronize the cellular events associated with these three core functions. The new and exciting findings on the Nek family open new perspectives and should allow the Neks to finally claim the attention they deserve in the field of kinases and cell cycle biology.
除了Polo激酶和Aurora激酶外，参与有丝分裂调控的第三个但研究较少的激酶家族是NIMA相关激酶（Neks）。该家族的创始成员是构巢曲霉的唯一成员NIMA，它对该生物体中有丝分裂的起始至关重要。所有11种人类Neks已根据在哺乳动物中为该家族确定的三个核心功能之一进行了功能分配：（1）中心粒/有丝分裂；（2）初级纤毛功能/纤毛病；（3）DNA损伤反应（DDR）。然而，最近的研究发现，特别是关于Nek 1和Nek 8的研究发现，几种Neks至少在其中两种情况下并行参与：初级纤毛功能和DDR。在这篇深入综述的核心部分，我们报告了目前关于11种Neks中每一种的详细功能知识。在讨论中，我们回到Neks之间的交叉联系，并指出我们和其他研究小组的功能和相互作用组学研究如何揭示，大多数Neks与与这三种功能背景中的两种（如果不是全部三种）相关的蛋白质伙伴相互作用。然后我们提出一个假设，即Neks可能是连接调节元件，使细胞能够微调并同步与这三种核心功能相关的细胞事件。关于Nek家族的新的和令人兴奋的发现开辟了新的视角，应该能让Neks最终在激酶和细胞周期生物学领域获得应有的关注。
