“Stop Ne(c)king around”: How interactomics contributes to functionally characterize Nek family kinases  

作　　者：Gabriela Vaz Meirelles Arina Marina Perez Edmárcia Elisa de Souza Ferna Luisa Basei Priscila Ferreira Papa Talita Diniz Melo Hanchuk Vanessa Bomfim Cardoso Jrg Kobarg 

机构地区：[1]Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP 13084-971,Brazil [2]Departamento de Bioquímica-Programa de Pós-gradua o em Biologia Funcional e Molecular, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP 13084-971, Brasil [3]Departamento de Genética, Evolu o e Bioagentes-Programa de Pós-gradua o em Genética e Biologia Molecular, Instituto de Biologia, Universidade Estadual de Campinas,1 Campinas, SP 13084-97, Brasil

出　　处：《World Journal of Biological Chemistry》2014年第2期141-160,共20页世界生物化学杂志（英文版）（电子版）

基　　金：Supported by Fundao de AmparoàPesquisa do Estado S o Paulo(FAPESP,Grant No.2010/51730-0);Conselho Nacional de Pesquisa e Desenvolvimento(CNPq);Centro Nacional de Pesquisa em Energia e Materiais(CNPEM)

摘　　要：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.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.

关 键 词：Cell cycle MITOSIS DNA damage response Protein interactions KINASES 

分 类 号：Q55[生物学—生物化学]