Ubiquitin-dependent Degradation of Id1 and Id3 is Mediated by the COP9 Signalosome

Berse, Matthias; Bounpheng, Mangkey A.; Huang, Xiaohua; Christy, Barbara A.; Pollmann, Christian; Dubiel, Wolfgang

doi:10.1016/j.jmb.2004.08.043

Cited by 54 publications

(36 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We report that CSN-5 contains a conserved MAPK D site and that CSN-5 interacts both physically and genetically with KGB-1. The suggestion of a protective role for CSN-5 regarding GLH-1 is also based on other researchers reporting a protective role for the mammalian CSN-5 homolog, which protects c-Jun, Id1 and Id3, as well as our finding that loss of C. elegans CSN-5 closely mimics loss of GLH-1 and GLH-4 (Berse et al, 2004;Naumann et al, 1999;Smith et al, 2002).…”

Section: Csn-5 As a Protective Partnersupporting

confidence: 83%

GLH-1, theC. elegansP granule protein, is controlled by the JNK KGB-1 and by the COP9 subunit CSN-5

Orsborn

McEwen

et al. 2007

Development

View full text Add to dashboard Cite

The GLHs (germline RNA helicases) are constitutive components of the germline-specific P granules in the nematode Caenorhabditis elegansand are essential for fertility, yet how GLH proteins are regulated remains unknown. KGB-1 and CSN-5 are both GLH binding partners, previously identified by two-hybrid interactions. KGB-1 is a MAP kinase in the Jun N-terminal kinase(JNK) subfamily, whereas CSN-5 is a subunit of the COP9 signalosome. Intriguingly, although loss of either KGB-1 or CSN-5 results in sterility,their phenotypes are strikingly different. Whereas csn-5 RNA interference (RNAi) results in under-proliferated germlines, similar to glh-1/glh-4(RNAi), the kgb-1(um3) loss-of-function mutant exhibits germline over-proliferation. When kgb-1(um3) mutants are compared with wild-type C. elegans, GLH-1 protein levels are as much as 6-fold elevated and the organization of GLH-1 in P granules is grossly disrupted. A series of additional in vivo and in vitro tests indicates that KGB-1 and CSN-5 regulate GLH-1 levels, with GLH-1 targeted for proteosomal degradation by KGB-1 and stabilized by CSN-5. We propose the `good cop: bad cop' team of CSN-5 and KGB-1 imposes a balance on GLH-1 levels, resulting in germline homeostasis. In addition, both KGB-1 and CSN-5 bind Vasa, a Drosophila germ granule component; therefore, similar regulatory mechanisms might be conserved from worms to flies.

show abstract

Section: Csn-5 As a Protective Partnersupporting

confidence: 83%

GLH-1, theC. elegansP granule protein, is controlled by the JNK KGB-1 and by the COP9 subunit CSN-5

Orsborn

McEwen

et al. 2007

Development

View full text Add to dashboard Cite

show abstract

“…This discrepancy might be due to modulation of fluorescence intensity by interactions between EGFP and UPP-related proteins. 24 Moreover, neuritic beading of mitochondria was also induced by nontagged UbB þ 1 (Figure 3c). Taken together, these observations indicate that the demonstrated neuritic effects were specific to UbB þ 1.…”

Section: Discussionmentioning

confidence: 91%

Mutant ubiquitin found in Alzheimer's disease causes neuritic beading of mitochondria in association with neuronal degeneration

et al. 2007

View full text Add to dashboard Cite

A dinucleotide deletion in human ubiquitin (Ub) B messenger RNA leads to formation of polyubiquitin (UbB) þ 1, which has been implicated in neuronal cell death in Alzheimer's and other neurodegenerative diseases. Previous studies demonstrate that UbB þ 1 protein causes proteasome dysfunction. However, the molecular mechanism of UbB þ 1-mediated neuronal degeneration remains unknown. We now report that UbB þ 1 causes neuritic beading, impairment of mitochondrial movements, mitochondrial stress and neuronal degeneration in primary neurons. Transfection of UbB þ 1 induced a buildup of mitochondria in neurites and dysregulation of mitochondrial motor proteins, in particular, through detachment of P74, the dynein intermediate chain, from mitochondria and decreased mitochondria-microtubule interactions. Altered distribution of mitochondria was associated with activation of both the mitochondrial stress and p53 cell death pathways. These results support the hypothesis that neuritic clogging of mitochondria by UbB þ 1 triggers a cascade of events characterized by local activation of mitochondrial stress followed by global cell death. Furthermore, UbB þ 1 small interfering RNA efficiently blocked expression of UbB þ 1 protein, attenuated neuritic beading and preserved cellular morphology, suggesting a potential neuroprotective strategy for certain neurodegenerative disorders.

show abstract

“…A plausible explanation is that Id proteins could inactivate the ubiquitin proteasome system and affect the degradation of Aurora A in our study. Id1 could bind to various components of the 26S proteasome including the S5A subunit of the 19S proteasome (Anand et al, 1997;Hasskarl et al, 2007) and the JAB1 protein (Berse et al, 2004). The S5A subunit contains an ubiquitin-interacting motif domain involved in the recognition and shuttling of the polyubiquitinated substrates to the proteolytic 20S degradation chamber of the proteasome (Hershko and Ciechanover, 1998).…”

Section: Discussionmentioning

confidence: 99%

Id1 Overexpression Induces Tetraploidization and Multiple Abnormal Mitotic Phenotypes by Modulating Aurora A

Man¹,

Rosa

Yip³

et al. 2008

MBoC

View full text Add to dashboard Cite

The basic helix-loop-helix transcription factor, Id1, was shown to induce tetraploidy in telomerase-immortalized nasopharyngeal epithelial cells in this study. Using both transient and stable Id1-expressing cell models, multiple mitotic aberrations were detected, including centrosome amplification, binucleation, spindle defects, and microtubule perturbation. Many of these abnormal phenotypes have previously been reported in cells overexpressing Aurora A. Further experiments showed that Id1 could stabilize Aurora A, whereas knocking down Aurora A expression in Id1-expressing cells could rescue some of the mitotic defects. The mechanisms by which Aurora A could be modulated by Id1 were explored. DNA amplification of the Aurora A locus was not involved. Id1 could only weakly activate the transcriptional activity of the Aurora A promoter. We found that Id1 overexpression could affect Aurora A degradation, leading to its stabilization. Aurora A is normally degraded from mitosis exit by the APC/C Cdh1 -mediated proteasomal proteolysis pathway. Our results revealed that Id1 and Cdh1 are binding partners. The association of Id1 and Cdh1 was found to be dependent on the canonical destruction box motif of Id1, the increased binding of which may compete with the interaction between Cdh1 and Aurora A, leading to stabilization of Aurora A in Id1-overexpressing cells.

show abstract

Ubiquitin-dependent Degradation of Id1 and Id3 is Mediated by the COP9 Signalosome

Cited by 54 publications

References 43 publications

GLH-1, theC. elegansP granule protein, is controlled by the JNK KGB-1 and by the COP9 subunit CSN-5

GLH-1, theC. elegansP granule protein, is controlled by the JNK KGB-1 and by the COP9 subunit CSN-5

Mutant ubiquitin found in Alzheimer's disease causes neuritic beading of mitochondria in association with neuronal degeneration

Id1 Overexpression Induces Tetraploidization and Multiple Abnormal Mitotic Phenotypes by Modulating Aurora A

Contact Info

Product

Resources

About