{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Garcia-Rendueles AR"],"funding":["Medical Research Council","Rosetrees"],"pagination":["6354-6368"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8585666"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["40(45)"],"pubmed_abstract":["It is unclear how loss-of-function germline mutations in the widely-expressed co-chaperone AIP, result in young-onset growth hormone secreting pituitary tumours. The RET receptor, uniquely co-expressed in somatotrophs with PIT1, induces apoptosis when unliganded, while RET supports cell survival when it is bound to its ligand. We demonstrate that at the plasma membrane, AIP is required to form a complex with monomeric-intracellular-RET, caspase-3 and PKCδ resulting in PIT1/CDKN2A-ARF/p53-apoptosis pathway activation. AIP-deficiency blocks RET/caspase-3/PKCδ activation preventing PIT1 accumulation and apoptosis. The presence or lack of the inhibitory effect on RET-induced apoptosis separated pathogenic AIP variants from non-pathogenic ones. We used virogenomics in neonatal rats to demonstra"],"journal":["Oncogene"],"pubmed_title":["RET signalling provides tumorigenic mechanism and tissue specificity for AIP-related somatotrophinomas."],"pmcid":["PMC8585666"],"funding_grant_id":["MR/M018539/1","M505"],"pubmed_authors":["Oroz-Gonjar F","Suarez-Farina M","Solomou A","Garcia-Rendueles AR","Dieguez C","Korbonits M","Pradilla-Dieste A","Chenlo M","Barry S","Perez-Romero S","Garcia-Lavandeira M","Alvarez CV","Mistry A","Mehlen P","Gaston-Massuet C"],"additional_accession":[]},"is_claimable":false,"name":"RET signalling provides tumorigenic mechanism and tissue specificity for AIP-related somatotrophinomas.","description":"It is unclear how loss-of-function germline mutations in the widely-expressed co-chaperone AIP, result in young-onset growth hormone secreting pituitary tumours. The RET receptor, uniquely co-expressed in somatotrophs with PIT1, induces apoptosis when unliganded, while RET supports cell survival when it is bound to its ligand. We demonstrate that at the plasma membrane, AIP is required to form a complex with monomeric-intracellular-RET, caspase-3 and PKCδ resulting in PIT1/CDKN2A-ARF/p53-apoptosis pathway activation. AIP-deficiency blocks RET/caspase-3/PKCδ activation preventing PIT1 accumulation and apoptosis. The presence or lack of the inhibitory effect on RET-induced apoptosis separated pathogenic AIP variants from non-pathogenic ones. We used virogenomics in neonatal rats to demonstra","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Nov","modification":"2026-05-08T14:35:29.518Z","creation":"2022-02-11T13:10:39.845Z"},"accession":"S-EPMC8585666","cross_references":{"pubmed":["34588620"],"doi":["10.1038/s41388-021-02009-8"]}}