Yeast UBL-UBA proteins have partially redundant functions in cell cycle control

Laura A Díaz-Martínez,Duncan J Clarke,Kylie J Walters,Yang Kang

doi:10.1186/1747-1028-1-28

Laura A Díaz-Martínez, Duncan J Clarke + Show 2 more

Open Access

https://doi.org/10.1186/1747-1028-1-28

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Journal: Cell Division	Publication Date: Dec 1, 2006
Citations: 80	License type: cc-by

Affiliation: University of Minnesota

Abstract

BackgroundProteins containing ubiquitin-like (UBL) and ubiquitin associated (UBA) domains have been suggested to shuttle ubiquitinated substrates to the proteasome for degradation. There are three UBL-UBA containing proteins in budding yeast: Ddi1, Dsk2 and Rad23, which have been demonstrated to play regulatory roles in targeting ubiquitinated substrates to the proteasome for degradation. An involvement of these proteins in cell cycle related events has also been reported. We tested whether these three proteins act redundantly in the cell cycle.ResultsHere we show that the UBL-UBA proteins are partially redundant for cell cycle related roles. RAD23 is redundant with DDI1 and DSK2, but DDI1 and DSK2 are not redundant with each other and the triple deletion shows a synthetic effect, suggesting the existence of at least two roles for RAD23 in cell cycle control. The rad23Δddi1Δdsk2Δ triple deletion strain delays both in G2/M-phase and in mid-anaphase at high temperatures with duplicated spindle pole bodies. Cell cycle progression in the triple deletion strain can only be partially rescued by a rad23 allele lacking the c-terminal UBA domain, suggesting that RAD23 requires its c-terminal UBA domain for full function. In addition to their ability to bind ubiquitin and the proteasome, the UBL-UBA proteins also share the ability to homodimerize. Rad23 and Dsk2 dimerization requires their UBL and/or UBA domains whereas Ddi1 dimerization does not. Here we show that Ddi1 homodimerization is necessary for its cell cycle related functions.ConclusionThe three yeast UBL-UBA proteins have partially redundant roles required for progression through mitosis.

Highlights

Proteins containing ubiquitin-like (UBL) and ubiquitin associated (UBA) domains have been suggested to shuttle ubiquitinated substrates to the proteasome for degradation
RAD23, DDI1 and DSK2 have partially redundant roles in cell cycle progression Possible roles for Rad23 and Ddi1 in the cell cycle have been suggested by their ability to rescue the temperature sensitivity of pds1–128 [31], while Rad23 and Dsk2 have been reported to have roles in Spindle Pole Body (SPB) duplication and Dsk2 overexpression leads to mitotic arrest [28]
Cell cycle distribution in the ddi1Δdsk2Δ double deletion was not different from those of the single deletions. These results suggest that RAD23 is redundant with DDI1 and DSK2 but that DDI1 and DSK2 do not share a common functional role needed for timely cell cycle progression

Summary

Introduction

Proteins containing ubiquitin-like (UBL) and ubiquitin associated (UBA) domains have been suggested to shuttle ubiquitinated substrates to the proteasome for degradation. There are three UBL-UBA containing proteins in budding yeast: Ddi, Dsk and Rad, which have been demonstrated to play regulatory roles in targeting ubiquitinated substrates to the proteasome for degradation An involvement of these proteins in cell cycle related events has been reported. Rad homo and heterodimerization of UBL-UBA family members has been suggested to play a role in regulating their interactions with other components of the ubiquitin-proteasome pathway and to lead to the formation of multimeric complexes with polyubiquitin chains [23,25] Such interactions could increase the targeting efficiency of ubiquitinated substrates for degradation

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