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Cdc48 and Ufd3, new partners of the ubiquitin protease Ubp3, are required for ribophagy.

ABSTRACT: Ubiquitin-dependent processes can be antagonized by substrate-specific deubiquitination enzymes involved in many cellular functions. In this study, we show that the yeast Ubp3-Bre5 deubiquitination complex interacts with both the chaperone-like Cdc48, a major actor of the ubiquitin and proteasome system, and Ufd3, a ubiquitin-binding cofactor of Cdc48. We observed that these partners are required for the Ubp3-Bre5-dependent and starvation-induced selective degradation of yeast mature ribosomes, also called ribophagy. By contrast, proteasome-dependent degradation does not participate in this process. Our data favour the idea that these factors cooperate to recognize and deubiquitinate specific substrates of ribophagy before their vacuolar degradation.

SUBMITTER: Ossareh-Nazari B

PROVIDER: S-EPMC2897114 | biostudies-other | 2010 Jul

REPOSITORIES: biostudies-other

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Publications

Cdc48 and Ufd3, new partners of the ubiquitin protease Ubp3, are required for ribophagy.

Ossareh-Nazari Batool B Bonizec Mélanie M Cohen Mickael M Dokudovskaya Svetlana S Delalande François F Schaeffer Christine C Van Dorsselaer Alain A Dargemont Catherine C

EMBO reports 20100528 7

Ubiquitin-dependent processes can be antagonized by substrate-specific deubiquitination enzymes involved in many cellular functions. In this study, we show that the yeast Ubp3-Bre5 deubiquitination complex interacts with both the chaperone-like Cdc48, a major actor of the ubiquitin and proteasome system, and Ufd3, a ubiquitin-binding cofactor of Cdc48. We observed that these partners are required for the Ubp3-Bre5-dependent and starvation-induced selective degradation of yeast mature ribosomes, ...[more]

PMID: 20508643

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Project description:UnlabelledThe androgen receptor (AR) is a key transcription factor in the initiation and progression of prostate cancer (PC) and is a major therapeutic target for the treatment of advanced disease. Unfortunately, current therapies are not curative for castration resistant PC and a better understanding of AR regulation could identify novel therapeutic targets and biomarkers to aid treatment of this disease. The AR is known to be regulated by a number of post-translational modifications and we have recently identified the deubiquitinating enzyme Usp12 as a positive regulator of AR. We determined that Usp12 deubiquitinates the AR resulting in elevated receptor stability and activity. Furthermore, Usp12 silencing was shown to reduce proliferation of PC cells.Usp12 is known to require the co-factors Uaf-1 and WDR20 for catalytic activity. In this report we focus further on the role of Uaf-1 and WDR20 in Usp12 regulation and investigate if these co-factors are also required for controlling AR activity. Firstly, we confirm the presence of the Usp12/Uaf-1/WDR20 complex in PC cells and demonstrate the importance of Uaf-1 and WDR20 for Usp12 stabilisation. Consequently, we show that individual silencing of either Uaf-1 or WDR20 is sufficient to abrogate the activity of the Usp12 complex and down-regulate AR-mediated transcription via receptor destabilisation resulting in increased apoptosis and decreased colony forming ability of PC cells. Moreover, expression of both Uaf-1 and WDR20 is higher in PC tissue compared to benign controls. Overall these results highlight the potential importance of the Usp12/Uaf-1/WDR20 complex in AR regulation and PC progression.Highlights• Androgen receptor is a key transcriptional regulator in prostate cancer • Usp12/Uaf-1/WDR20 complex plays a crucial role in androgen receptor stability and activity • Destabilising an individual Usp12/Uaf-1/WDR20 complex member reduces the protein levels of the whole complex and diminishes androgen receptor activity • Protein levels of all members of the Usp12/Uaf-1/WDR20 complex are significantly increased in PC.

Dataset Information

Cdc48 and Ufd3, new partners of the ubiquitin protease Ubp3, are required for ribophagy.

Publications

Cdc48 and Ufd3, new partners of the ubiquitin protease Ubp3, are required for ribophagy.

Similar Datasets

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