Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1.
COP9 signalosome (CSN) cleaves the ubiquitin-like protein Nedd8 from the Cul1 subunit of SCF ubiquitin ligases. The Jab1/MPN domain metalloenzyme (JAMM) motif in the Jab1/Csn5 subunit was found to underlie CSN's Nedd8 isopeptidase activity. JAMM is found in proteins from archaea, bacteria, and eukaryotes, including the Rpn11 subunit of the 26S proteasome. Metal chelators and point mutations within JAMM abolished CSN-dependent cleavage of Nedd8 from Cul1, yet had little effect on CSN complex assembly. Optimal SCF activity in yeast and both viability and proper photoreceptor cell (R cell) development in Drosophila melanogaster required an intact Csn5 JAMM domain. We propose that JAMM isopeptidases play important roles in a variety of physiological pathways.
Department of Biology, California Institute of Technology (CalTech), Pasadena, CA 91125, USA.
Gregory A
GA
Cope
Greg S B
GS
Suh
L
L
Aravind
Sylvia E
SE
Schwarz
S Lawrence
SL
Zipursky
Eugene V
EV
Koonin
Raymond J
RJ
Deshaies
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000075686:COP9 Signalosome Complex; D019759:Carbon-Nitrogen Lyases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D044842:Cullin Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D000075687:NEDD8 Protein; D010447:Peptide Hydrolases; D010453:Peptide Synthases / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013696:Temperature; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
C100988:Cdc53 protein, S cerevisiae; D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; C513173:Nedd8 protein, Drosophila; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D014452:Ubiquitins; D044843:SKP Cullin F-Box Protein Ligases; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; C501491:CSN5 protein, Drosophila; D000075686:COP9 Signalosome Complex; D008666:Metalloendopeptidases; C468276:Rri1 protein, S cerevisiae; D019759:Carbon-Nitrogen Lyases; C034300:isopeptidase; D010453:Peptide Synthases