{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE343nnn/GSE343793/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE343793"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"p53 engagement is a hallmark of an unfolded protein response in the nucleus of mammalian cells","description":"Exposure to exogenous and endogenous stress is associated with the intracellular accumulation of aberrant unfolded and misfolded proteins. In eukaryotic cells, protein homeostasis within membrane-bound organelles is regulated by specialized signaling pathways, with the unfolded protein response in the endoplasmic reticulum serving as a foundational example. Yet, it is unclear if a similar surveillance mechanism exists in the nucleus. Here we leveraged engineered proteins called destabilizing domains to acutely expose mammalian cells to nuclear- or cytosolic- localized unfolded protein. We show that the appearance of unfolded protein in either compartment engages a common transcriptional response associated with the transcription factors Nrf1 and Nrf2. Uniquely, only in the nucleus does unfolded protein activate a robust p53-driven transcriptional response and a transient p53-independent cell cycle delay. These studies highlight the distinct effects of localized protein folding stress and the unique protein quality control environment of the nucleus.","dates":{"publication":"2026/08/31"},"accession":"GSE343793","cross_references":{"GSM":["GSM9962728","GSM9962729","GSM9962693","GSM9962694","GSM9962695","GSM9962696","GSM9962730","GSM9962697","GSM9962731","GSM9962698","GSM9962732","GSM9962699","GSM9962733","GSM9962734","GSM9962735","GSM9962736","GSM9962737","GSM9962738","GSM9962717","GSM9962718","GSM9962719","GSM9962720","GSM9962721","GSM9962722","GSM9962723","GSM9962724","GSM9962725","GSM9962726","GSM9962727","GSM9962706","GSM9962707","GSM9962708","GSM9962709","GSM9962750","GSM9962751","GSM9962752","GSM9962710","GSM9962711","GSM9962712","GSM9962713","GSM9962714","GSM9962715","GSM9962716","GSM9962739","GSM9962740","GSM9962741","GSM9962742","GSM9962743","GSM9962744","GSM9962700","GSM9962745","GSM9962701","GSM9962746","GSM9962702","GSM9962703","GSM9962747","GSM9962704","GSM9962748","GSM9962749","GSM9962705"],"GPL":["24247"],"GSE":["343793"],"taxon":["Mus musculus"]}}