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.

Abstract

The cellular functions of the product of the Saccharomyces cerevisiae ANC1 (actin non-complementing) gene were investigated. ANC1 was previously identified in a screen for mutations that enhance the defect caused 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 defects in the organization of the actin cytoskeleton and the localization of Spa2p, a protein implicated in polarity development and cytokinesis. Morphological abnormalities exhibited by anc1 mutants include failure to form a mating projection in response to alpha-factor and development of swollen or elongated cell shapes during proliferation. These morphological aberrations correlate with cytoskeletal defects that were also observed. These phenotypes demonstrate that Anc1p is important for actin function and for the functions of other proteins involved in morphogenesis. In further support of these roles for Anc1p, the anc1 delta 1::HIS3 mutation was found to be synthetically lethal in combination 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 subset of acute lymphoblastic leukemias, acute myeloid leukemias, and lymphomas. Our findings suggest that changes in the functions or organization of actin filaments might contribute to the establishment of the neoplastic state for these leukemias and lymphomas.