{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Funk AL"],"funding":["Intramural NIH HHS","NCI NIH HHS"],"pubmed_abstract":["The worldwide frequency of head and neck squamous cell carcinoma (HNSCC) is approximately 800,000 new cases, with 430,000 deaths annually. We determined that LZK (encoded by <i>MAP3K13</i>) is a therapeutic target in HNSCC and showed that inhibition with small molecule inhibitors decreases the viability of HNSCC cells with amplified <i>MAP3K13</i>. A drug-resistant mutant of LZK blocks decreases in cell viability due to LZK inhibition, indicating on-target activity by two separate small molecules. Inhibition of LZK catalytic activity suppressed tumor growth in HNSCC PDX models with amplified <i>MAP3K13</i>. We found that the kinase activity of LZK stabilized c-MYC and that LZK stabilized gain-of-function (GOF) p53 through a kinase-independent mechanism. Therefore, we designed proteolysis-t"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.11.19.623840"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11601640"],"repository":["biostudies-literature"],"pubmed_title":["Targeting GOF p53 and c-MYC through LZK Inhibition or Degradation Suppresses Head and Neck Tumor Growth."],"pmcid":["PMC11601640"],"funding_grant_id":["ZIA BC011691","HHSN261201500003I","HHSN261201500003C"],"pubmed_authors":["Karpinska K","Chang TC","Swenson RE","Ahel I","Funk AL","James A","Ries AL","Marusiak AA","Cappell SD","Afifi M","Rubin MR","Difilippantonio S","Katerji M","Edwards ZC","Bergman KL","Gough NR","Robinson CM","Chen L","Trotter EW","Dash S","Doroshow JH","Woodroofe CC","Brognard J","Karim BO","Xu X","Nyswaner K","Lindberg E"],"additional_accession":[]},"is_claimable":false,"name":"Targeting GOF p53 and c-MYC through LZK Inhibition or Degradation Suppresses Head and Neck Tumor Growth.","description":"The worldwide frequency of head and neck squamous cell carcinoma (HNSCC) is approximately 800,000 new cases, with 430,000 deaths annually. We determined that LZK (encoded by <i>MAP3K13</i>) is a therapeutic target in HNSCC and showed that inhibition with small molecule inhibitors decreases the viability of HNSCC cells with amplified <i>MAP3K13</i>. A drug-resistant mutant of LZK blocks decreases in cell viability due to LZK inhibition, indicating on-target activity by two separate small molecules. Inhibition of LZK catalytic activity suppressed tumor growth in HNSCC PDX models with amplified <i>MAP3K13</i>. We found that the kinase activity of LZK stabilized c-MYC and that LZK stabilized gain-of-function (GOF) p53 through a kinase-independent mechanism. Therefore, we designed proteolysis-t","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2025-04-04T12:01:20.17Z","creation":"2025-04-04T12:01:20.17Z"},"accession":"S-EPMC11601640","cross_references":{"pubmed":["39605563"],"doi":["10.1101/2024.11.19.623840"]}}