{"doi":"10.1016/j.jcmgh.2020.11.010","title":"Protein Lysine Acetylation","abstract":"The factors that contribute to acute pancreatitis development and modulate its severity continue to be described. In addition to acute injury, chronic cell injury and inflammation, such as seen in chronic pancreatitis, increases the risk of developing pancreatic cancer. To meet its major physiologic functions to produce, store, and release digestive enzymes, the pancreatic acinar cell has exceptionally high rates of protein synthesis. This makes it particularly susceptible to endoplasmic stress responses, a process that can contribute to the pathogenesis of pancreatitis and pancreatic cancer. The study by Cooley et al1Cooley M.M. Thomas D.D.H. Deans K. et al.Deficient endoplasmic reticulum acetyl-CoA import in pancreatic acinar cells leads to chronic pancreatitis.Cell Mol Gastroenterol Hepatol. 2021; 11: 725-738Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar in this issue of Cellular and Molecular Gastroenterology and Hepatology highlights how important acetylation of lysine resides on nascent proteins is to acinar function and its links to ER stress. Although the work is done in the context of pancreatic acinar cell responses, the findings likely have relevance to other gastrointestinal tissues. During synthesis, nascent secretory proteins are translocated into the lumen of the endoplasmic reticulum (ER) and there undergo an exquisitely orchestrated process of modification and folding that results in a preprotein or mature protein. This time- and energy-dependent process is monitored by a family of ER quality control proteins that sense proper protein folding; if that is the case, the protein is then allowed to advance in the secretory pathway. If not, responses are first activated that work to globally improve protein folding; if this fails, an ER stress response is triggered that can lead to cell injury, elaboration of inflammatory mediators, and even cell death. Protein misfolding can occur for many reasons including defects in amino acid sequences, failure to properly form disulfide bonds, and changes in the milieu of the ER including its energetics and calcium levels. Several major cotranslational and post-translational modifications of nascent protein, such as phosphorylation and ubiquitylation, are frequently needed for functionality. Such modifications can have a range of biologic effects that include cellular targeting, biologic activity, protein stability, and protein-protein interactions. Although described more than 50 years ago, the functional and cellular effects of protein acetylation on surface exposed lysine residues of nascent proteins has been much less studied and is the topic examined by Cooley et al.1Cooley M.M. Thomas D.D.H. Deans K. et al.Deficient endoplasmic reticulum acetyl-CoA import in pancreatic acinar cells leads to chronic pancreatitis.Cell Mol Gastroenterol Hepatol. 2021; 11: 725-738Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar The importance of this study is that it highlights a previously undescribed role for protein acetylation in acinar cell physiology and disease and makes several key observations. First, mRNA levels of a key modulator of protein acetylation, AT-1, which mediates the transport of acetyl-CoA into the ER lumen, are regulated (upregulated with physiologic stimulation of acinar cells, and downregulated during pancreatitis). Others have found that AT-1 levels determine the degree of protein acetylation and that both increased and decreased levels can result in cell pathology.2Dieterich I.A. Lawton A.J. Peng Y. et al.Acetyl-CoA flux regulates the proteome and acetyl-proteome to maintain intracellular metabolic crosstalk.Nat Commun. 2019; 10: 3929Crossref PubMed Scopus (14) Google Scholar That the levels of AT-1 can be dynamically regulated is an important insight that should prompt the examination of this pathway in many systems and a more detailed examination in the pancreas. Second, global reduction of AT-1 activity or targeted deletion o","journal":"Cellular and Molecular Gastroenterology and Hepatology","year":2020,"id":114171,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":494516,"name":"Fred S. Gorelick","orcid":"0000-0001-8293-6803","position":0,"is_corresponding":true}],"reference_count":4,"raw_metadata":null,"created_at":"2026-07-18T23:13:29.674622Z","pmid":"33279460","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}