FHA-RING ubiquitin ligases in cell division cycle control.
Despite the common occurrence of forkhead associated (FHA) phosphopeptide-binding domains and really interesting new gene (RING) E3 ubiquitin ligase domains, gene products containing both an N-terminal FHA domain and C-terminal RING domain constitute a highly distinctive intersection. Characterized FHA-RING ligases include the two vertebrate proteins, Checkpoint with FHA and RING (Chfr) and RING finger 8 (Rnf8), as well as three fungal proteins, Defective in mitosis (Dma1), Chf1 and Chf2. These FHA-RING ligases play roles in negative regulation of the cell division cycle, apparently by coupling protein phosphorylation events to specific ubiquitylation of target proteins. Here, the available data on upstream and downstream regulation of and by FHA-RING ligases are reviewed.
Brooks
L
L
Departments of Genetics and Biochemistry and Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03756, USA.
Heimsath
E G
EG
Loring
G L
GL
Brenner
C
C
D051722:ADAM Proteins / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology; D018816:Genes, cdc; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology; D000075223:Poly-ADP-Ribose Binding Proteins; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology; D012568:Schizosaccharomyces / Q000166:cytology; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000502:physiology; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D025521:Tumor Suppressor Proteins / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000502:physiology*; D054875:Ubiquitination
C493791:Cdc123 protein, S cerevisiae; D018797:Cell Cycle Proteins; C493793:DMA2 protein, S cerevisiae; D004268:DNA-Binding Proteins; C493792:Dma1 protein, S cerevisiae; C103134:Dma1 protein, S pombe; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C486521:RNF8 protein, human; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D025521:Tumor Suppressor Proteins; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases; D051722:ADAM Proteins; C090222:ADAM11 protein, human