{"doi":"10.1016/j.celrep.2021.109706","title":"ATF3 promotes the serine synthesis pathway and tumor growth under dietary serine restriction","abstract":"The serine synthesis pathway (SSP) involving metabolic enzymes phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) drives intracellular serine biosynthesis and is indispensable for cancer cells to grow in serine-limiting environments. However, how SSP is regulated is not well understood. Here, we report that activating transcription factor 3 (ATF3) is crucial for transcriptional activation of SSP upon serine deprivation. ATF3 is rapidly induced by serine deprivation via a mechanism dependent on ATF4, which in turn binds to ATF4 and increases the stability of this master regulator of SSP. ATF3 also binds to the enhancers/promoters of PHGDH, PSAT1, and PSPH and recruits p300 to promote expression of these SSP genes. As a result, loss of ATF3 expression impairs serine biosynthesis and the growth of cancer cells in the serine-deprived medium or in mice fed with a serine/glycine-free diet. Interestingly, ATF3 expression positively correlates with PHGDH expression in a subset of TCGA cancer samples.","journal":"Cell Reports","year":2021,"id":150053,"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":98,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":638143,"name":"Daniel E. Gracilla","orcid":"0000-0002-4849-5538","position":1,"is_corresponding":false},{"id":499468,"name":"Lun Cai","orcid":"0000-0002-4717-2390","position":2,"is_corresponding":false},{"id":638144,"name":"Mingyi Zhang","orcid":"0000-0002-9996-6774","position":3,"is_corresponding":false},{"id":638145,"name":"Xiaolin Yu","orcid":"0000-0001-9532-3598","position":4,"is_corresponding":false},{"id":277603,"name":"Xiaoguang Chen","orcid":"0000-0003-2035-4431","position":5,"is_corresponding":false},{"id":356390,"name":"Junran Zhang","orcid":"0000-0001-5413-3675","position":6,"is_corresponding":false},{"id":555968,"name":"Xiaochun Long","orcid":"0000-0001-9714-0023","position":7,"is_corresponding":false},{"id":242439,"name":"Han‐Fei Ding","orcid":"0000-0001-5702-3439","position":8,"is_corresponding":false},{"id":277604,"name":"Chunhong Yan","orcid":"0000-0002-3974-7991","position":9,"is_corresponding":false},{"id":638142,"name":"Xingyao Li","orcid":"0000-0003-4245-680X","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-18T23:43:01.325389Z","pmid":"34551291","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":[]}