{"doi":"10.1002/mc.23356","title":"Sulforaphane covalently interacts with the transglutaminase 2 cancer maintenance protein to alter its structure and suppress its activity","abstract":"Type 2 transglutaminase (TG2) functions as an important cancer cell survival protein in a range of cancers including epidermal squamous cell carcinoma. TG2 exists in open and closed conformations each of which has a distinct and mutually exclusive activity. The closed conformation has GTP-binding/GTPase activity while the open conformation functions as a transamidase to catalyze protein-protein crosslinking. GTP-binding/GTPase activity is required for TG2 maintenance of the aggressive cancer phenotype. Thus, identifying agents that convert TG2 from the closed to the open GTP-binding/GTPase inactive conformation is an important cancer prevention/treatment strategy. Sulforaphane (SFN) is an important diet-derived cancer prevention agent that is known to possess a reactive isothiocyanate group and has potent anticancer activity. Using a biotin-tagged SFN analog (Biotin-ITC) and kinetic analysis we show that SFN covalently and irreversibly binds to recombinant TG2 to inhibit transamidase activity and shift TG2 to an open/extended conformation, leading to a partial inhibition of GTP binding. We also show that incubation of cancer cells or cancer cell extract with Biotin-ITC results in formation of a TG2/Biotin-ITC complex and that SFN treatment of cancer cells inhibits TG2 transamidase activity and shifts TG2 to an open/extended conformation. These findings identify TG2 as a direct SFN anticancer target in epidermal squamous cell carcinoma.","journal":"Molecular Carcinogenesis","year":2021,"id":181534,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"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":732484,"name":"Gautam Adhikary","orcid":"0009-0004-7082-5742","position":1,"is_corresponding":false},{"id":500661,"name":"Henryk Szmacinski","orcid":"0009-0007-7600-2714","position":2,"is_corresponding":false},{"id":361304,"name":"Joseph R. Lakowicz","orcid":"0000-0003-3032-3620","position":3,"is_corresponding":false},{"id":379328,"name":"David J. Weber","orcid":"0000-0002-8824-1110","position":4,"is_corresponding":false},{"id":471206,"name":"Raquel Godoy‐Ruiz","orcid":"0000-0003-4569-0781","position":5,"is_corresponding":false},{"id":733172,"name":"Puranik Purushottamachar","orcid":null,"position":6,"is_corresponding":false},{"id":732485,"name":"Jeffrey W. Keillor","orcid":"0000-0002-8133-6862","position":7,"is_corresponding":false},{"id":732486,"name":"Eric W. J. Gates","orcid":"0000-0003-3381-2200","position":8,"is_corresponding":false},{"id":732487,"name":"Richard L. Eckert","orcid":"0000-0002-3770-4779","position":9,"is_corresponding":false},{"id":733171,"name":"Ellen A. Rorke","orcid":null,"position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T23:48:05.146883Z","pmid":"34610184","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":[]}