Due to the high recurrence rates of Cushing’s disease, nonsurgical medical therapies are frequently used. However, there were few medicinal interventions available that targeted corticotroph adenomas. Identification of corticotroph lineage-specific proteins that are implicated in Cushing’s tumor phenotype was required to create a therapy that mainly targets corticotrophs in Cushing’s disease.
For a study, researchers stated that corticotrophs from mice used as models for Cushing’s illness had higher expression levels of E2F transcription factor 1 (E2F1), one of the proteins that control the cell cycle. E2F1 was also linked to the control of POMC gene expression. It had been proposed that E2F1’s Ser337 phosphorylation (pS337-E2F1), which made it easier to attach to the POMC promoter, was a factor in corticotrophs’ increased POMC production. They demonstrated that E2F1 expression in healthy human pituitaries is exclusive to the corticotroph lineage and that the E2F1 protein is located in the cytosol in healthy corticotrophs. In addition, they demonstrated that, in contrast to the normal pituitary, where pS337-E2F1 is found in the perinuclear cytoplasm, Cushing’s tumors exclusively localize the protein in the nucleus.
The finding showed that pS337 is a marker for Cushing’s tumors and implied that phosphorylation of E2F1 may be a target for creating a novel pharmaceutical therapy for tumorigenesis and hormone imbalance in Cushing’s disease.