A protein–protein interaction map of the <i>Caenorhabditis elegans</i> 26S proteasome

Davy, Anne; Bello, Paul; Thierry‐Mieg, Nicolas; Vaglio, Philippe; Hitti, Joseph; Doucette‐Stamm, Lynn; Thierry-Mieg, Danielle; Reboul, Jérôme; Boulton, Simon J.; Walhout, Albertha J.M.; Coux, Olivier; Vidal, Marc

doi:10.1093/embo-reports/kve184

Cited by 174 publications

(117 citation statements)

References 29 publications

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“…In various systems, RPN-12 has been shown to function in the regulatory particle of the proteasome and was proposed to share some activities with the subunit RPN-10 ( Wilkinson et al 2000;Glickman and Ciechanover 2002;Takahashi et al 2002). In C. elegans, only 3 of the 30 genes shown so far to encode proteasome subunits (Davy et al 2001) do not result in embryonic lethality upon disruption by RNAi: rpn-9, rpn-10, and rpn-12 (Takahashiet al 2002;Kamath et al 2003;Sonnichsen et al 2005). While we did not identify rpn-9 or rpn-10 in the genomewide screen, subsequent analysis revealed that RNAi from either of these two genes can also suppress par-2(it5ts) embryonic lethality (Table 1), albeit less efficiently than RNAi from rpn-12.…”

Section: Resultsmentioning

confidence: 99%

A Genomewide Screen for Suppressors of par-2 Uncovers Potential Regulators of PAR Protein-Dependent Cell Polarity in Caenorhabditis elegans

Labbé

Pacquelet²,

Marty³

et al. 2006

Genetics

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The PAR proteins play an essential role in establishing and maintaining cell polarity. While their function is conserved across species, little is known about their regulators and effectors. Here we report the identification of 13 potential components of the C. elegans PAR polarity pathway, identified in an RNAi-based, systematic screen to find suppressors of par-2(it5ts) lethality. Most of these genes are conserved in other species. Phenotypic analysis of double-mutant animals revealed that some of the suppressors can suppress lethality associated with the strong loss-of-function allele par-2(lw32), indicating that they might impinge on the PAR pathway independently of the PAR-2 protein. One of these is the gene nos-3, which encodes a homolog of Drosophila Nanos. We find that nos-3 suppresses most of the phenotypes associated with loss of par-2 function, including early cell division defects and maternal-effect sterility. Strikingly, while PAR-1 activity was essential in nos-3; par-2 double mutants, its asymmetric localization at the posterior cortex was not restored, suggesting that the function of PAR-1 is independent of its cortical localization. Taken together, our results identify conserved components that regulate PAR protein function and also suggest a role for NOS-3 in PAR protein-dependent cell polarity.

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Section: Resultsmentioning

confidence: 99%

A Genomewide Screen for Suppressors of par-2 Uncovers Potential Regulators of PAR Protein-Dependent Cell Polarity in Caenorhabditis elegans

Labbé

Pacquelet²,

Marty³

et al. 2006

Genetics

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“…To date, we do not know whether this rapid turnover is inherent to the protein or involves specific degradation mechanisms. One interesting hint for this question is that the homologue of Nsa2 in Caenorhabditis elegans (Q9XTD3) interacts in two-hybrid with the Rpn10 subunit of the proteasome (20). Hence, when pre-60 S biogenesis is impaired, Nsa2 might be targeted to the proteasome degradation pathway.…”

Section: Discussionmentioning

confidence: 99%

Nsa2 Is an Unstable, Conserved Factor Required for the Maturation of 27 SB Pre-rRNAs

Lebreton¹,

Saveanu

Decourty

et al. 2006

Journal of Biological Chemistry

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In Saccharomyces cerevisiae, a large variety of pre-ribosomal factors have been identified recently, a number of which are still of unknown function. The essential pre-ribosomal 30-kDa protein, Nsa2, was characterized as one of the most conserved proteins from yeast to human. We show here that the expression of the human orthologue TINP1 complements the repression of NSA2 in yeast. Nsa2 was co-purified in several pre-ribosomal complexes and found to be essential for the large ribosomal subunit biogenesis. Like several other factors of the pre-60 S particles, the absence of Nsa2 correlated with a decrease in the 25 S and 5.8 S ribosomal RNA levels, and with an accumulation of 27 SB pre-ribosomal RNA intermediates. We show that Nsa2 is a functional partner of the putative GTPase Nog1. In the absence of Nsa2, Nog1 was still able to associate with pre-ribosomal complexes blocked in maturation. In contrast, in the absence of Nog1, Nsa2 disappeared from pre-60 S complexes. Indeed, when ribosome biogenesis was blocked upstream of Nsa2, this short half-lived protein was largely depleted, suggesting that its cellular levels are tightly regulated.Ribosome biogenesis is a highly conserved process among eukaryotes and results in the synthesis of functional small and large ribosomal subunits, necessary for the translation of mRNAs into proteins in the cytoplasm. This essential process is tightly regulated; indeed, in exponentially growing Saccharomyces cerevisiae cells, it accounts for about 60% of the metabolic effort (1), whereas it is almost completely turned off during the stationary phase.The pathway begins with the transcription by RNA polymerase I of a 35 S ribosomal RNA (rRNA) precursor and of the 5 S rRNA by RNA polymerase III. This transcription, together with the nuclear import of ribosomal proteins, pre-ribosomal factors, and small nucleolar RNAs, is responsible for the self-assembly of the nucleolus (reviewed in Ref.2), a region of the nucleus specialized in the production of ribosomes. Association of ribosomal proteins and pre-ribosomal factors with nascent pre-rRNAs gives birth to a 90 S pre-ribosomal complex, which undergoes various steps of maturation, first in the nucleolus, then in the nucleoplasm, and finally in the cytoplasm after export through the pores of the nuclear envelope (for a review of the whole pathway, see . Along this maturation, the 90 S complex separates into a pre-60 S complex, which will generate the large ribosomal subunit containing mature 25 S, 5.8 S, and 5 S rRNAs, and a pre-40 S complex, which will generate the small ribosomal subunit containing 18 S rRNA. A large number of factors are necessary for the correct modification, cleavage, and processing of pre-rRNAs, the positioning of ribosomal proteins, and the export of the pre-60 S and pre-40 S particles toward the cytoplasm.More than 100 factors associated with pre-60 S complexes (pre-60 S factors) have been identified to date, a number of which remain to be characterized (4, 6 -9). Some of them display obvious enzymatic functions ...

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“…Like TRC8, Hrd1/der3p is a multi-membrane spanning ER resident protein containing a RING-H2 ®nger with E3-ubiquitin ligase activity (Deak and Wolf, 2001;Bays et al, 2001). Using a yeast 2-hybrid screen, Hrd1/der3p was found to interact with the proteasome lid subunit, Rpn11 (Davy et al, 2001), which is the direct counterpart to JAB1 (Voges et al, 1999). This suggests that TRC8 may be somewhat analogous to the Hrd1/der3p protein complex in the ER, perhaps targeting a subset of proteins for degradation in a VHL-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

The TRC8 hereditary kidney cancer gene suppresses growth and functions with VHL in a common pathway

et al. 2002

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VHL is part of an SCF related E3-ubiquitin ligase complex with`gatekeeper' function in renal carcinoma. However, no mutations have been identi®ed in VHL interacting proteins in wild type VHL tumors. We previously reported that the TRC8 gene was interrupted by a t(3;8) translocation in a family with hereditary renal and non-medullary thyroid cancer. TRC8 encodes a multi-membrane spanning protein containing a RING-H2 ®nger with in vitro ubiquitin ligase activity. We isolated the Drosophila homologue, DTrc8, and studied its function by genetic manipulations and a yeast 2-hybrid screen. Human and Drosophila TRC8 proteins localize to the endoplasmic reticulum. Loss of either DTrc8 or DVhl resulted in an identical ventral midline defect. Direct interaction between DTrc8 and DVhl was con®rmed by GST-pulldown and co-immunoprecipitation experiments. CSN-5/JAB1 is a component of the COP9 signalosome, recently shown to regulate SCF function. We found that DTrc8 physically interacts with CSN-5 and that human JAB1 localization is dependent on VHL mutant status. Lastly, overexpression of DTrc8 inhibited growth consistent with its presumed role as a tumor suppressor gene. Thus, VHL, TRC8, and JAB1 appear to be linked both physically and functionally and all three may participate in the development of kidney cancer.

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A protein–protein interaction map of the Caenorhabditis elegans 26S proteasome

Cited by 174 publications

References 29 publications

A Genomewide Screen for Suppressors of par-2 Uncovers Potential Regulators of PAR Protein-Dependent Cell Polarity in Caenorhabditis elegans

A Genomewide Screen for Suppressors of par-2 Uncovers Potential Regulators of PAR Protein-Dependent Cell Polarity in Caenorhabditis elegans

Nsa2 Is an Unstable, Conserved Factor Required for the Maturation of 27 SB Pre-rRNAs

The TRC8 hereditary kidney cancer gene suppresses growth and functions with VHL in a common pathway

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