A Deubiquitinating Enzyme That Disassembles Free Polyubiquitin Chains Is Required for Development but Not Growth in Dictyostelium

• Published in: The Journal of biological chemistry 1998-10, Vol.273 (44), p.29178-29187
• Main Authors: Lindsey, David F., Amerik, Alexander, Deery, William J., Bishop, John D., Hochstrasser, Mark, Gomer, Richard H.
• Format: Article
• Language: English
• Subjects: ACTIVIDAD ENZIMATICA; ACTIVITE ENZYMATIQUE; Amino Acid Sequence; AMINO ACID SEQUENCES; AMP; Animals; ARN MENSAJERO; ARN MESSAGER; Base Sequence; Biopolymers - metabolism; C-AMP; CELL DIFFERENTIATION; CHEMICAL COMPOSITION; CHEMOTAXIS; COMPOSICION QUIMICA; COMPOSITION CHIMIQUE; CRECIMIENTO; CROISSANCE; Cyclic AMP - metabolism; Cysteine Endopeptidases - metabolism; DEGRADACION; DEGRADATION; Deubiquitinating enzymes; DICTYOSTELIUM; Dictyostelium - enzymology; Dictyostelium - growth & development; DIFERENCIACION CELULAR; DIFFERENCIATION CELLULAIRE; DNA Primers; Endopeptidases - chemistry; Endopeptidases - genetics; Endopeptidases - metabolism; ENZYMIC ACTIVITY; EXPRESION GENICA; EXPRESSION DES GENES; GENBANK/U48271; GENE; GENE EXPRESSION; Gene Expression Regulation; GENES; GROWTH; INTRONS; MECANISME CHIMIOTACTIQUE; MESSENGER RNA; MOLECULAR SEQUENCE DATA; Multienzyme Complexes - metabolism; MUTANT; MUTANTES; MUTANTS; NUCLEOTIDE SEQUENCE; OPEN READING FRAMES; POLIMEROS; POLYMERE; POLYMERS; Polyubiquitin; polyubiquitin chains; PROTEASAS; PROTEASE; PROTEASES; Proteasome Endopeptidase Complex; PROTEINAS; PROTEINE; PROTEINS; Protozoan Proteins; QUIMIOTACTISMO; SECUENCIA NUCLEOTIDICA; SEQUENCE NUCLEOTIDIQUE; STRUCTURAL GENES; THIOL PROTEINASES; Ubiquitins - metabolism; UBPA GENE; UbpA protein
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.44.29178

Although cell differentiation usually involves synthesis of new proteins, little is known about the role of protein degradation. In eukaryotes, conjugation to ubiquitin polymers often targets a protein for destruction. This process is regulated by deubiquitinating enzymes, which can disassemble ubiquitin polymers or ubiquitin-substrate conjugates. We find that a deubiquitinating enzyme, UbpA, is required for Dictyostelium development.ubpA cells have normal protein profiles on gels, grow normally, and show normal responses to starvation such as differentiation and secretion of conditioned medium factor. However,ubpA cells have defective aggregation, chemotaxis, cAMP relay, and cell adhesion. These defects result from low expression of cAMP pulse-induced genes such as those encoding the cAR1 cAMP receptor, phosphodiesterase, and the gp80 adhesion protein. Treatment of ubpA cells with pulses of exogenous cAMP allows them to aggregate and express these genes like wild-type cells, but they still fail to develop fruiting bodies. Unlike wild type, ubpAcells accumulate ubiquitin-containing species that comigrate with ubiquitin polymers, suggesting a defect in polyubiquitin metabolism. UbpA has sequence similarity with yeast Ubp14, which disassembles free ubiquitin chains. Yeast ubp14 cells have a defect in proteolysis, due to excess ubiquitin chains competing for substrate binding to proteasomes. Cross-species complementation and enzyme specificity assays indicate that UbpA and Ubp14 are functional homologs. We suggest that specific developmental transitions in Dictyostelium require the degradation of specific proteins and that this process in turn requires the disassembly of polyubiquitin chains by UbpA.