title: New interaction partners for Nek4.1 and Nek4.2 isoforms: from the DNA damage response to RNA splicing.
abstract: BACKGROUND
  Neks are serine-threonine kinases that are similar to NIMA, a protein found in Aspergillus nidulans which is essential for cell division. In humans there are eleven Neks which are involved in different biological functions besides the cell cycle control. Nek4 is one of the largest members of the Nek family and has been related to the primary cilia formation and in DNA damage response. However, its substrates and interaction partners are still unknown. In an attempt to better understand the role of Nek4, we performed an interactomics study to find new biological processes in which Nek4 is involved. We also described a novel Nek4 isoform which lacks a region of 46 amino acids derived from an insertion of an Alu sequence and showed the interactomics profile of these two Nek4 proteins.
  
  
  CONCLUSIONS
  Isoform 1 and isoform 2 of Nek4 were expressed in human cells and after an immunoprecipitation followed by mass spectrometry, 474 interacting proteins were identified for isoform 1 and 149 for isoform 2 of Nek4. About 68% of isoform 2 potential interactors (102 proteins) are common between the two Nek4 isoforms. Our results reinforce Nek4 involvement in the DNA damage response, cilia maintenance and microtubule stabilization, and raise the possibility of new functional contexts, including apoptosis signaling, stress response, translation, protein quality control and, most intriguingly, RNA splicing. We show for the first time an unexpected difference between both Nek4 isoforms in RNA splicing control. Among the interacting partners, we found important proteins such as ANT3, Whirlin, PCNA, 14-3-3ε, SRSF1, SRSF2, SRPK1 and hNRNPs proteins.
  
  
  CONCLUSIONS
  This study provides new insights into Nek4 functions, identifying new interaction partners and further suggests an interesting difference between isoform 1 and isoform 2 of this kinase. Nek4 isoform 1 may have similar roles compared to other Neks and these roles are not all preserved in isoform 2. Besides, in some processes, both isoforms showed opposite effects, indicating a possible fine controlled regulation.
authors: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Rua Giuseppe Máximo Scolfaro 10.000, C.P.6192, 13084-971 Campinas, São Paulo Brazil ; Programa de Pós-graduação em Biologia Funcional e Molecular, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo Brazil.
authors: Fernanda Luisa
authors: FL
authors: Basei
authors: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Rua Giuseppe Máximo Scolfaro 10.000, C.P.6192, 13084-971 Campinas, São Paulo Brazil.
authors: Gabriela Vaz
authors: GV
authors: Meirelles
authors: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Rua Giuseppe Máximo Scolfaro 10.000, C.P.6192, 13084-971 Campinas, São Paulo Brazil.
authors: Germanna Lima
authors: GL
authors: Righetto
authors: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Rua Giuseppe Máximo Scolfaro 10.000, C.P.6192, 13084-971 Campinas, São Paulo Brazil ; Programa de Pós-graduação em Genética e Biologia Molecular, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo Brazil.
authors: Deivid Lucas
authors: DL
authors: Dos Santos Migueleti
authors: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Rua Giuseppe Máximo Scolfaro 10.000, C.P.6192, 13084-971 Campinas, São Paulo Brazil.
authors: Juliana Helena Costa
authors: JH
authors: Smetana
authors: Programa de Pós-graduação em Biologia Funcional e Molecular, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo Brazil ; Programa de Pós-graduação em Genética e Biologia Molecular, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo Brazil ; Instituto de Biologia, Departamento de Bioquímica e de Biologia Tecidual, Universidade Estadual de Campinas, Campinas, SP Brazil ; Universidade Estadual de Campinas, Faculdade de Ciências Farmacêuticas, Campinas, São Paulo Brazil.
authors: Jörg
authors: J
authors: Kobarg
keywords: Apoptosis; DNA damage response; Interactomics; Neks; mRNA processing