p38 MAPK pathway-dependent SUMOylation of Elk-1 and phosphorylation of PIAS2 correlate with the downregulation of Elk-1 activity in heat-stressed HeLa cells

Abstract

Stress-activated and mitogen-activated protein kinases (MAPKs) regulate gene expression by post-translational modifications of transcription factors. Elk-1, a transcription factor that regulates the expression of immediate early genes, is amenable to regulation by all the three mammalian MAPKs. In the present report, using inhibitors specific for different MAPK pathways, we show that during exposure of HeLa cells to heat stress, Elk-1 is SUMOylated with SUMO1 by p38 MAPK pathway-dependent mechanisms. Elk-1phosphorylation levels were significantly reduced under similar conditions. We also show that transcriptional activity of Elk-1 as assessed by luciferase reporter expression and qPCR estimation of the expression of genes regulated by Elk-1 was downregulated upon exposure to heat stress; this downregulation was reversed when heat exposure was performed in the presence of either SB203580 (p38 MAPK inhibitor) or ginkgolic acid (inhibitor of SUMOylation). Elk-1 induced transcription is also regulated by PIAS2 which acts as a coactivator upon the activation of extracellular signal-regulated kinases (ERKs) and as a corepressor upon its phosphorylation by p38 MAPK. Since heat stress activates the p38 MAPK pathway, we determined if PIAS2 was phosphorylated in heat-stressed HeLa cells. Our studies indicate that in HeLa cells exposed to heat stress, PIAS2 is phosphorylated by p38 MAPK pathway-dependent mechanisms. Collectively, the results presented demonstrate that in heat-stressed HeLa cells, p38 MAPK pathway-dependent SUMOylation of Elk-1 and phosphorylation of PIAS2 correlate with the downregulation of transactivation by Elk-1.

Neuronal activity‐induced SUMOylation of Akt1 by PIAS3 is required for long‐term potentiation of synaptic transmission

“…The SUMO ligases are demonstrated to facilitate the conjugations of SUMOs and substrates. The SUMO ligase PIASs family, including PIAS1, PIAS2, PIAS3, and PIAS4, are required for the SUMOylation of various proteins 34‐39 . In this study, our results reveal that neuronal activity promotes the interaction of Akt1 with PIAS1 and PIAS3, but has no effect on the binding between Akt1 with PIAS2 and PIAS4.…”

“…The SUMO ligase PIASs family, including PIAS1, PIAS2, PIAS3, and PIAS4, are required for the SUMOylation of various proteins. [34][35][36][37][38][39] In this study, our results reveal that neuronal activity promotes the interaction of Akt1 with PIAS1 and PIAS3, but has no effect on the binding between Akt1 with PIAS2 and PIAS4. Previously, PIAS1 has been reported to mediate SUMO1 conjugation at Akt1 K276 residue in vitro and in insulin-stimulated cancer cell line, which contributes to cancer cell proliferation and tumor progression.…”

Transcriptional Analyses of Acute Exposure to Methylmercury on Erythrocytes of Loggerhead Sea Turtle

“…The enzyme that encodes the PIAS2 gene contains two structural motifs (finger ring and SUMO binding) and one domain (SAP domain) that activate or repress the Elk-1 transcription factor, which depends on the MAPK pathway [ 128 , 129 , 130 ]. The Elk-1 transcription factor has been shown to bind to the promoters of almost 1000 genes, including IE genes (genes for rapid response to growth factors and other stimuli), genes encoding the basal transcription machinery, spliceosome components, and ribosomal proteins [ 129 ]. PIAS2 is a transcriptional co-regulator that activates or represses the transcription of at least 60 proteins.…”

MicroRNA‐150 and its target ETS‐domain transcription factor 1 contribute to inflammation in diabetic photoreceptors

“…Our results suggest that HFD/PA may induce inflammation in photoreceptors by increasing nuclear pELK1 S383 , and the upregulated cytoplasmic pELK1 S383 could further exacerbate the inflammation. While phosphorylated ELK1 promotes the transcription of downstream genes, SUMOylated ELK1 represses the transactivation activity 54,55 . Stress elevates the phosphorylation of ELK1 but removing the SUMOylation 56,57 .…”