A NUCLEAR-PROTEIN WITH SEQUENCE SIMILARITY TO PROTEINS IMPLICATED IN HUMAN ACUTE LEUKEMIAS IS IMPORTANT FOR CELLULAR MORPHOGENESIS AND ACTIN CYTOSKELETAL FUNCTION IN SACCHAROMYCES-CEREVISIAE

The cellular functions of the product of the Saccharomyces cerevisiae ANC1 (actin noncomplementing) gene were investigated. ANC1 was previou sly identified in a screen for mutations that enhance the defect cause d by a mutation in the actin gene. Here, we show that anc1-1 and anc1 Delta 1::HIS3 (gene deletion) mutants exhibit a novel combination of d efects in the organization of the actin cytoskeleton and the localizat ion of Spa2p, a protein implicated in polarity development and cytokin esis. Morphological abnormalities exhibited by and mutants include fai lure to form a mating projection in response to ct-factor and developm ent of swollen or elongated cell shapes during proliferation. These mo rphological aberrations correlate with cytoskeletal defects that were also observed. These phenotypes demonstrate that Anc1p is important fo r actin function and for the functions of other proteins involved in m orphogenesis. In further support of these roles for Anc1p, the anc1 De lta 1::HIS3 mutation was found to be synthetically lethal in combinati on with a null mutation in SLA1, a gene that is important for membrane cytoskeleton function. Surprisingly, Anc1p was found to be a nuclear protein and to have sequence similarity to the human proteins ENL and AF-9. These human proteins are implicated in the development of a subs et of acute lymphoblastic leukemias, acute myeloid leukemias, and lymp homas. Our findings suggest that changes in the functions or organizat ion of actin filaments might contribute to the establishment of the ne oplastic state for these leukemias and lymphomas.