Abstract
Members of the family of NEK kinases (NIMA related kinases) were identified as important regulators of cell cycle checkpoints, especially at the G2 to M phase transition. Although they are among all kinases one of the least studied families, recent studies showed they can have crucial roles in mitosis, centrosome disjunction, and in the signaling of the DNA damage response. These characteristics along with the fact that several NEKs were found to be over-expressed in cancer, or were shown to present elevated mutation rates, suggest that they are interesting candidates both in the diagnostic as well as in the therapy of cancer. However, for most NEKs the physiological substrates have not been identified and nor are the functional consequences of the found point mutations known that occur in their genes in cancer cells. Therefore, the central aim of this project is to elucidate the functional roles of the NEKs in normal and tumoral cells. We will use the "Shokat" approach to generate kinase that are sensitive to ATP analogs to identify physiological substrates of the NEKs. Furthermore, we will generate mutations observed in Nek genes in cancer tissues to analyze functional consequences of these altered kinases in vitro and in vivo. Furthermore, we will characterize the protein expression of NEKs in normal and tumor tissues and 'high throughput screening' of inhibitors, based on coupled kinase/luciferase ATP consumption bioassay, previously developed in our group. In summary, our project envisions to study the physiological and pathophysiological roles of NEK 1, 3, 4, 5, 6, 7, 8 and 10. The studies will contribute to explore the potential of these cell cycle regulatory kinases as novel targets in the therapy of cancer and envision the discovery of novel anti-cancer inhibitors. (AU)
Scientific publications
(7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FEREZIN, CAMILA DE CASTRO;
BASEI, FERNANDA LUISA;
MELO-HANCHUK, TALITA D.;
DE OLIVEIRA, ANA LUISA;
PERES DE OLIVEIRA, ANDRESSA;
MORI, MATEUS P.;
DE SOUZA-PINTO, NADJA C.;
KOBARG, JORG.
NEK5 interacts with LonP1 and its kinase activity is essential for the regulation of mitochondrial functions and mtDNA maintenance.
FEBS OPEN BIO,
v. 11,
n. 3
FEB 2021.
Web of Science Citations: 0.
CASTELUCCI, B. G.;
PEREIRA, A. H. M.;
FIORAMONTE, M.;
CARAZZOLLE, M. F.;
DE OLIVEIRA, P. S. L.;
FRANCHINI, K. G.;
KOBARG, J.;
MARTINS-DE-SOUZA, D.;
JOAZEIRO, P. P.;
CONSONNI, S. R.
Evidence of macrophage modulation in the mouse pubic symphysis remodeling during the end of first pregnancy and postpartum.
SCIENTIFIC REPORTS,
v. 10,
n. 1
JUL 24 2020.
Web of Science Citations: 0.
PERES DE OLIVEIRA, ANDRESSA;
BASEI, FERNANDA LUISA;
SLEPICKA, PRISCILA FERREIRA;
DE CASTRO FEREZIN, CAMILA;
MELO-HANCHUK, TALITA D.;
DE SOUZA, EDMARCIA ELISA;
LIMA, TANES I.;
DOS SANTOS, VALQUIRIA TIAGO;
MENDES, DAVI;
SILVEIRA, LEONARDO REIS;
MENCK, CARLOS FREDERICO MARTINS;
KOBARG, JORG.
NEK10 interactome and depletion reveal new roles in mitochondria.
PROTEOME SCIENCE,
v. 18,
n. 1
APR 28 2020.
Web of Science Citations: 0.
DE OLIVEIRA, ANDRESSA PERES;
ISSAYAMA, LUIDY KAZUO;
BETIM PAVAN, ISADORA CAROLINA;
SILVA, FERNANDO RIBACK;
MELO-HANCHUK, TALITA DINIZ;
SIMABUCO, FERNANDO MOREIRA;
KOBARG, JORG.
Checking NEKs: Overcoming a Bottleneck in Human Diseases.
Molecules,
v. 25,
n. 8
APR 2 2020.
Web of Science Citations: 1.
ALVES BARBOSA, EVERTON DE ALMEIDA;
SERAPHIM, THIAGO VARGAS;
GANDIN, CESAR AUGUSTO;
TEIXEIRA, LEILANE FERREIRA;
GONCALVES DA SILVA, RONNI ANDERSON;
RIGHETTO, GERMANNA L.;
GONCALVES, KALIANDRA DE ALMEIDA;
VASCONCELLOS, RAPHAEL DE SOUZA;
ALMEIDA, MARCIA ROGERIA;
SILVA JUNIOR, ABELARDO;
RANGEL FIETTO, JULIANA LOPES;
KOBARG, JORG;
GILEADI, CARINA;
MASSIRER, KATLIN B.;
BORGES, JULIO CESAR;
NETO, MARIO DE OLIVEIRA;
BRESSAN, GUSTAVO COSTA.
Insights into the full-length SRPK2 structure and its hydrodynamic behavior.
International Journal of Biological Macromolecules,
v. 137,
p. 205-214,
SEP 15 2019.
Web of Science Citations: 0.