NEK6

NEK6

A gene on chromosome 9q33.3-q34.11 that encodes a NEK serine/threonine protein kinase that plays a key role in cell cycle progression and is required for chromosome segregation at metaphase-anaphase transition, mitotic spindle formation and cytokinesis. NEK6 phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, RPS6KB1, TRIP4, STAT3, histones H1 and H3, and KIF11 to promote mitotic spindle formation. It is involved in G2/M-phase cell cycle arrest induced by DNA damage, the inhibition of which results in apoptosis. It may contribute to tumourigenesis by suppressing p53/TP53-induced cancer cell senescence. It is upregulated by NEK9 and interacts with ANKRA2, ATF4, APBB1, ARHGAP33, CDC42, CIR1, KIF11, PRAM1, PTN, PRDX3, PIN1, RAD26L, RBBP6, RPS6KB1, RPS7, STAT3 and TRIP4.
References in periodicals archive ?
Song et al., "Nek6 overexpression antagonizes p53-induced senescence in human cancer cells," Cell Cycle, vol.
However, Nek6 and Nek7 are smaller molecules and consist only of a catalytic domain with a moderately short N-terminal expansion.
In this context, we elucidate the structural information of Nek6, which may be a new drug target for developing inhibitors against cancers by means of a homology modeling approach pursued by a molecular dynamic simulation in order to explore the stability of the protein.
The constructed Nek6 structure was validated by the inspection of phi/psi distributions of Ramachandran plot obtained through PROCHECK analysis [16].
The active sites (binding pockets) and functional residues of Nek6 were identified and characterized by Site-Map module from Schrodinger package [22].
The virtual screening workflow (Maestro, Schrodinger, 2009) [24] was used to identify the potential small molecule inhibitors against putative active site of Nek6 protein.
A vdw scaling of 0.5 was used for nonpolar atoms of both Nek6 and lead compounds from HTVS.
Homology Modeling of Nek6 Protein and Its Validation.
The group of upregulated genes combined, among other: insulin-like growth factor 1 (Igf1); insulin induced gene 1 (Insig1); Ccne1; Nek6; fibroblast growth factor 2 (Fgf2); UDP glucuronosyltransferase 1 family, polypeptide A5 (Ugt5a1); annexin 1 (Anxa1).
Ccne1, Ccnb1, Pttg1, and Nek6 mRNAs were strongly upregulated, while expression of Ccnd1 mRNA during the examined period was comparable to the control.
There are several important mitosis restriction points, for example, formation of metaphase in equatorial plane or separation of sister chromatids during anaphase, in which Nek6 and Pttg1 genes play an important role.
Yang et al., "Clinical and biological significance of never in mitosis gene A-related kinase 6 (NEK6) expression in hepatic cell cancer," Pathology & Oncology Research, vol.