Function of Polo-like Kinase 3 in NF-κB-mediated Proapoptotic Response

Abstract

RelA, the p65 subunit of NF-B transcription factors, plays a key role in regulation of antiapoptotic and proapoptotic responses. However, the downstream target genes regulated by RelA-NF-B in the initiation of proapoptotic signaling were not identified. We previously showed that RelA-NF-B functioned as a proapoptotic factor by activating the p53-signaling pathway in response to doxycycline-induced superoxide. In the present study, we demonstrate that the ability of doxycycline/superoxide to induce expression of polo-like kinase 3 (Plk3) depends on NF-B activity. We

Doxycycline up-regulates the expression of IL-6 and GM-CSF via MAPK/ERK and NF-κB pathways in mouse thymic epithelial cells

“…Following activation, phosphorylation and degradation of IκBα drastically alter the dynamic balance between cytosolic and nuclear localization signals to allow the NF-κB heterodimer rapidly translocating to the nucleus, where it activates the transcription of target genes [40]. In accordance with previous reports of Dox as an activator of the NF-κB signal pathway [34,35], we observed a much elevated level of the phosphorylated p65 in MTEC1 cells treated with Dox (Fig. 3).…”

“…On the other hand, Dox has been shown to be an activator of the NF-κB signal pathway [34,35]. We wonder whether this pathway also contributes to Dox-mediated enhancement of cytokine production in Cell lysate was prepared, and the levels of phosphorylated p65 and total p65 were analyzed by Western blotting.…”

The in vivo gene expression signature of oxidative stress

“…While these genes were upregulated in untreated Sod1 Ϫ/Ϫ mice, none of them was upregulated in untreated Gpx1 Ϫ/Ϫ mice, which is a control because the Gpx1 Ϫ/Ϫ mice do not exhibit elevated oxidative damage. Two additional p53 transcriptional target genes, Btg2 (12,71) and Plk3 (55,89), are also in the list of genes in Table 3, while a third, Gadd45a (36,93), was not significantly induced in WT mice treated with diquat but was significantly induced (Ͼ5-fold) in Sod1 Ϫ/Ϫ mice treated with diquat (see Supplemental Table S1), suggesting that this gene is responsive to oxidative stress but only at very high levels of stress. Btg2 and Plk3 barely fell under the statistical cutoff in the untreated Sod1 Ϫ/Ϫ mice; on the other hand, the induction of these genes was dramatically higher in the Sod1 Ϫ/Ϫ and Gpx1 Ϫ/Ϫ mice treated with diquat compared with WT mice treated with diquat (Table 3).…”

Plk3 Interacts with and Specifically Phosphorylates VRK1 in Ser342, a Downstream Target in a Pathway That Induces Golgi Fragmentation

“…In addition, Plk3 expression is induced after mitogenic stimulation, and it is required for mitotic (28) and S-phase (48) entry. Plk3 also regulates Cdc25C (3,23,26) and the NF-B signaling pathway (19). VRK1 phosphorylates p53 in Thr18 (20,40), a residue phosphorylated in response to taxol, an inhibitor of microtubule polymerization (34).…”