Lea Sistonen — Page 2 | PubMed Health

PubMed2002

Multisite phosphorylation provides sophisticated regulation of transcription factors.

Reversible phosphorylation is a prevalent mechanism by which the activity of eukaryotic transcription factors is regulated rapidly in response to changes in the cellular environment. Accumulated evidence has expanded the concept of phosphorylation to a process that provides dynamic and precise tuning of the transactivating potential of a factor, rather than being a static on/off switch. In the case of transcription factors such as heat shock factor 1 (HSF1), p53 and nuclear factor of activated T cells (NFAT), multisite phosphorylation enables several effects to operate within a single factor, thereby functioning as a key to signal integration. Studies on these transcription factors illustrate recent progress in solving the dynamic nature of transcriptional regulation by multisite phosphorylation.

Animals↗

PubMedDate not supplied

Reperfusion but not acute ischemia in pig small intestine induces transcriptionally mediated heat shock response in situ.

BACKGROUND: Although there is data on the cytoprotective role of heat shock proteins in intestinal ischemia-reperfusion, the effects of ischemia and reperfusion per se on the small intestinal heat shock response have been poorly characterized. METHODS: Four female pigs were subjected to 60-min ischemia by superior mesenteric artery occlusion followed by 360-min reperfusion. Systemic and local hemodynamics were monitored. Samples from the jejunal mucosa and muscularis were obtained for histology and for time series molecular biologic analyses of heat shock transcription factor 1 (HSF1), hsp70 mRNA and Hsp70 protein. RESULTS: A 30-min reperfusion of jejunum after a preceding 1-hour ischemia results in a significantly increased DNA-binding activity of HSF1, in a 10-fold increase of hsp70 mRNA in the mucosal and in a 7-fold increase in the muscular layers. Translational activation and accumulation of Hsp70 protein occurs after 60 min of reperfusion in the intestine. Nevertheless, a 60-min ischemia inducing mucosal detachment does not induce the heat shock response at any level analyzed. CONCLUSIONS: Ischemia alone is insufficient to induce the heat shock response, whereas subsequent reperfusion induces the response via transcriptionally mediated induction of Hsp70 synthesis both in the mucosal and muscular layers.

Acute Disease↗