Dual recruitment of Cdc48 (p97)-Ufd1-Npl4 ubiquitin-selective segregase by small ubiquitin-like modifier protein (SUMO) and ubiquitin in SUMO-targeted ubiquitin ligase-mediated genome stability functions.
Protein modification by SUMO and ubiquitin critically impacts genome stability via effectors that "read" their signals using SUMO interaction motifs or ubiquitin binding domains, respectively. A novel mixed SUMO and ubiquitin signal is generated by the SUMO-targeted ubiquitin ligase (STUbL), which ubiquitylates SUMO conjugates. Herein, we determine that the "ubiquitin-selective" segregase Cdc48-Ufd1-Npl4 also binds SUMO via a SUMO interaction motif in Ufd1 and can thus act as a selective receptor for STUbL targets. Indeed, we define key cooperative DNA repair functions for Cdc48-Ufd1-Npl4 and STUbL, thereby revealing a new signaling mechanism involving dual recruitment by SUMO and ubiquitin for Cdc48-Ufd1-Npl4 functions in maintaining genome stability.
Department of Molecular Biology, The Scripps Research Institute, La, Jolla, CA 92037, USA.
Minghua
M
Nie
Aaron
A
Aslanian
John
J
Prudden
Johanna
J
Heideker
Ajay A
AA
Vashisht
James A
JA
Wohlschlegel
John R
JR
Yates
Michael N
MN
Boddy
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D042822:Genomic Instability / Q000502:physiology*; D011485:Protein Binding; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*; D000074405:Valosin Containing Protein
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004271:DNA, Fungal; C576270:Npl4 protein, S pombe; D025842:SUMO-1 Protein; D029702:Schizosaccharomyces pombe Proteins; D025801:Ubiquitin; C576269:Ufd1 protein, S pombe; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein