Abstract 2310 Unexpected mechanisms of ETV6 dysfunction in hematologic disease

• DOI: 10.1016/j.jbc.2024.107072
• Publication Date: 2024-03-25T22:19:51Z
• Authors: Glen Liszczak; Michael McConville; Toby Thomas; Ryan Beckner; Catherine Valadez; Yuh Min Chook; Stephen Chung
• Keywords: Hematologic disease

Germline and somatic missense mutations in the transcriptional repressor ETV6 are strongly associated with blood diseases, including thrombocytopenia leukemia. These dominant negative mutations, which scattered throughout DNA binding domain a functionally unannotated linker region, cause protein to mislocalize cytoplasm. We set out answer following question: why do seemingly unrelated similar mislocalization phenotypes? A combination of chemical, biochemical, cellular approaches revealed multiple unique mechanisms through disease disrupt proper localization. Our discoveries have: (i) inspired small molecule- genetics-based strategies rescue mutant localization function, (ii) enabled development new animal models for dysfunction disease, (iii) uncovered regulatory function. thank Cancer Prevention Research Institute Texas, Welch Foundation, National General Medical Sciences funding this work.