Proteolysis-independent regulation of the transcription factor Met4 by a single Lys 48-linked ubiquitin chain
- 20 June 2004
- journal article
- letter
- Published by Springer Nature in Nature Cell Biology
- Vol. 6 (7) , 634-641
- https://doi.org/10.1038/ncb1143
Abstract
The ubiquitin ligase SCFMet30 is required for cell cycle progression in budding yeast. The critical function of SCFMet30 is inactivation of the transcriptional activator Met4. Here we show that a single ubiquitin chain is attached to Met4 through lysine at position 163. Inhibition of Met4 ubiquitination by mutating lysine to arginine at this position constitutively activates, but does not stabilize, Met4. This supports a proteolysis-independent role of Cdc34–SCFMet30-catalysed Met4 ubiquitination. Surprisingly, the ubiquitin chain attached to Met4 is linked through Lys 48 in ubiquitin, a ubiquitin chain structure that is usually required for substrate targeting to the 26S proteasome. These results suggest that Lys 48-linked ubiquitin chains can have a regulatory role independent of proteolysis.Keywords
This publication has 31 references indexed in Scilit:
- Non-traditional Functions of Ubiquitin and Ubiquitin-binding ProteinsJournal of Biological Chemistry, 2003
- RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMONature, 2002
- TAK1 is a ubiquitin-dependent kinase of MKK and IKKNature, 2001
- Protein regulation by monoubiquitinNature Reviews Molecular Cell Biology, 2001
- Cell Cycle–Regulated Modification of the Ribosome by a Variant Multiubiquitin ChainCell, 2000
- Recognition of the polyubiquitin proteolytic signalThe EMBO Journal, 2000
- Noncanonical MMS2-Encoded Ubiquitin-Conjugating Enzyme Functions in Assembly of Novel Polyubiquitin Chains for DNA RepairCell, 1999
- THE UBIQUITIN SYSTEMAnnual Review of Biochemistry, 1998
- UBIQUITIN-DEPENDENT PROTEIN DEGRADATIONAnnual Review of Genetics, 1996
- A Ubiquitin Mutant with Specific Defects in DNA Repair and MultiubiquitinationMolecular and Cellular Biology, 1995