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Published August 5, 2011 | Accepted Version + Supplemental Material
Journal Article Open

The TFIIH Subunit Tfb3 Regulates Cullin Neddylation


Cullin proteins are scaffolds for the assembly of multisubunit ubiquitin ligases, which ubiquitylate a large number of proteins involved in widely varying cellular functions. Multiple mechanisms cooperate to regulate cullin activity, including neddylation of their C-terminal domain. Interestingly, we found that the yeast Cul4-type cullin Rtt101 is not only neddylated but also ubiquitylated, and both modifications promote Rtt101 function in vivo. Surprisingly, proper modification of Rtt101 neither correlated with catalytic activity of the RING domain of Hrt1 nor required the Nedd8 ligase Dcn1. Instead, ubiquitylation of Rtt101 was dependent on the ubiquitin-conjugating enzyme Ubc4, while efficient neddylation involves the RING domain protein Tfb3, a subunit of the transcription factor TFIIH. Tfb3 also controls Cul3 neddylation and activity in vivo, and physically interacts with Ubc4 and the Nedd8-conjugating enzyme Ubc12 and the Hrt1/Rtt101 complex. Together, these results suggest that the conserved RING domain protein Tfb3 controls activation of a subset of cullins.

Additional Information

© 2011 Elsevier Inc. Received 1 December 2010; revised 4 April 2011; accepted 16 May 2011. Published: August 4, 2011. Available online 4 August 2011. We thank C. Rupp, C. Zbinden and R. Oania for technical assistance, and B. Schulman and members of the Peter laboratory for helpful discussions. G. Rabut was recipient of a Human Frontier Science Program Long-Term fellowship and is currently supported by INSERM and Région Bretagne. Work in the Deshaies and Peter laboratories is supported by the Howard Hughes Medical Institute and by research grants from Oncosuisse, the Swiss National Science Foundation, and the ETH Zurich, respectively.

Attached Files

Accepted Version - nihms318107.pdf

Supplemental Material - mmc1.pdf


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