The study of an autocrine signal transduction pathway that represses cell proliferation in Dictyostelium discoideum
Nikravan, Natalie Neda
Master of Arts
Many secreted factors are believed to inhibit cell proliferation in certain tissues such as tumors; however, the identity and action of most of these factors remains unknown. The recent identification of two autocrine secreted factors, AprA and CfaD, that inhibit cell proliferation in Dictyostelium discoideum , has enabled further study of how these factors regulate cell proliferation in a simple model system. Similar to AprA, the loss of CfaD in Dictyostelium strains increases the rate of cell proliferation in shaking cultures and leads to large fruiting bodies with large spore masses. The overexpression of CfaD causes tall, thin stalks with small spore masses. Analysis of different cell lines suggests that AprA is required for extracellular CfaD to inhibit cell proliferation. In addition, a screen for second-site suppressors of the aprA OE phenotype led to the identification of the Ddcln2 gene that encodes a tripeptidyl peptidase I. Examination of several DdTPPI properties, including an enzymatic activity assay, suggests the possible involvement of DdTPPI in both the AprA and CfaD signal transduction pathways that negatively regulate cell proliferation.
Cellular biology; Biochemistry; Pure sciences; Biological sciences