Heat shock protein 70 binds its own messenger ribonucleic acid as part of a gene expression self-limiting mechanism.
Expression of heat shock proteins is a cellular response to a variety of stressors. HSP70, the major stress-induced heat shock protein, is involved in repair and protection after the insult. However, the prolonged presence of this protein is detrimental. Consequently, Hsp70 expression must be tightly regulated. We have previously shown an increase in the degradation of Hsp70 messenger ribonucleic acid (mRNA) paralleling the accumulation of HSP70. Incubation of cells with transcriptional and translational inhibitors after heat shock resulted in a significant reduction in Hsp70 mRNA degradation. These observations suggest that newly synthesized, stress-induced factors might be involved in the decay of Hsp70 mRNA. We found that HSP70 binds directly to Hsp70 mRNA, as demonstrated by immunoprecipitation. This observation was confirmed by RNA gel-shift assays. These results are evidence for a novel and likely direct interaction between HSP70 and Hsp70 mRNA in cells after stress. This interaction may be part of a self-limiting mechanism to reduce HSP70 production, thus avoiding potential toxic effects of this protein in the absence of stress.
Department of Surgery, Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Karthik
K
Balakrishnan
Antonio
A
De Maio
D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D018869:Heat-Shock Response; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D011233:Precipitin Tests; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic
D018840:HSP70 Heat-Shock Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D011691:Puromycin; D003513:Cycloheximide