BTB/POZ Domain Proteins Are Putative Substrate Adaptors for Cullin 3 Ubiquitin Ligases

Geyer, Rory; Wee, Susan; Anderson, Scott; Yates, John R.; Wolf, Dieter A

doi:10.1016/s1097-2765(03)00341-1

Cited by 301 publications

(293 citation statements)

References 35 publications

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“…Several BTB proteins have been shown to be substrate receptors for Cullin 3 ubiquitin ligases (CDL3s) (Geyer et al, 2003;Pintard et al, 2003;Xu et al, 2003;Kobayashi et al, 2004;Zhang et al, 2004). Because KEL-8 contains a BTB domain, it might interact directly with CUL-3, the C. elegans Cullin 3 orthologue.…”

Section: Kel-8 Interacts With the Cul-3 Subunit Of Cullin 3 Ubiquitinmentioning

confidence: 99%

“…BTB domain proteins have recently been shown to function as substrate receptors for CDL3 ubiquitin ligases (Furukawa et al, 2003;Geyer et al, 2003;Pintard et al, 2003;Xu et al, 2003;Zhang et al, 2004). The BTB domain of this new class of substrate receptor (e.g., MEL-26) interacts with the Cullin repeats of Cul3, analogous to the manner by which Skp1 interacts with Cul1 in the CDL1/SCF complex.…”

Section: Kel-8 Is a Substrate Receptor For Cdl3mentioning

confidence: 99%

“…Recently, CDL3s were found to regulate the meiosis/mitosis transition in C. elegans (Pintard et al, 2003;Xu et al, 2003). CDL3s assemble with BTB proteins, which are substrate receptors that directly bind to Cul3 without the aid of an adaptor (Deshaies, 1999;Joazeiro and Weissman, 2000;Geyer et al, 2003;Pintard et al, 2003;Xu et al, 2003). There are many known BTB proteins, suggesting the assembly of a diverse array of CDL3s, each with unique substrate specificity (Willems et al, 2004;Petroski and Deshaies, 2005).…”

Section: Introductionmentioning

confidence: 99%

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KEL-8 Is a Substrate Receptor for CUL3-dependent Ubiquitin Ligase That Regulates Synaptic Glutamate Receptor Turnover

Schaefer

Rongo

2006

MBoC

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The regulated localization of ␣-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors (AMPARs) to synapses is an important component of synaptic signaling and plasticity. Regulated ubiquitination and endocytosis determine the synaptic levels of AMPARs, but it is unclear which factors conduct these processes. To identify genes that regulate AMPAR synaptic abundance, we screened for mutants that accumulate high synaptic levels of the AMPAR subunit GLR-1 in Caenorhabditis elegans. GLR-1 is localized to postsynaptic clusters, and mutants for the BTB-Kelch protein KEL-8 have increased GLR-1 levels at clusters, whereas the levels and localization of other synaptic proteins seem normal. KEL-8 is a neuronal protein and is localized to sites adjacent to GLR-1 postsynaptic clusters along the ventral cord neurites. KEL-8 is required for the ubiquitin-mediated turnover of GLR-1 subunits, and kel-8 mutants show an increased frequency of spontaneous reversals in locomotion, suggesting increased levels of GLR-1 are present at synapses. KEL-8 binds to CUL-3, a Cullin 3 ubiquitin ligase subunit that we also find mediates GLR-1 turnover. Our findings indicate that KEL-8 is a substrate receptor for Cullin 3 ubiquitin ligases that is required for the proteolysis of GLR-1 receptors and suggest a novel postmitotic role in neurons for Kelch/CUL3 ubiquitin ligases. INTRODUCTIONGlutamate is the most abundant excitatory neurotransmitter in the brain, and glutamatergic synapses play a critical role in learning, memory, and developmental plasticity of the central nervous system (Meldrum, 2000). Ionotropic glutamate receptors (GluRs) receive and transduce glutamatergic signals on the postsynaptic face of synapses, where these multitransmembrane spanning proteins assemble into tetrameric glutamate-gated channels of differing subunit composition (Hollmann and Heinemann, 1994;Dingledine et al., 1999). The regulation of these receptors, the ␣-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) type in particular, is a critical mechanism by which neurons modulate synaptic strength (Bredt and Nicoll, 2003;Malenka, 2003;Malinow, 2003;Sheng and Hyoung Lee, 2003). In addition, GluRs play a role in several diseases of the nervous system, ranging from neurodegeneration to drug addiction and schizophrenia (Tzschentke, 2002;Mattson, 2003;Moghaddam, 2003;Aarts and Tymianski, 2004). To better understand how AMPA-type GluRs (AMPARs) function in the nervous system, it is essential to determine how the synaptic level and activity of AMPARs are regulated.AMPAR synaptic levels are controlled by proteins that interact with signaling elements on the carboxy-terminal tail sequences that are exposed to the cytosol (Dong et al., 1997;Rongo et al., 1998;Song et al., 1998;Srivastava et al., 1998;Xia et al., 1999;Sans et al., 2001). Although some of the tail sequence signaling elements function to maintain high levels of AMPARs at the synapse, other signaling elements recruit factors that result in the ubiquitination, endocytosis, ...

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Section: Kel-8 Interacts With the Cul-3 Subunit Of Cullin 3 Ubiquitinmentioning

confidence: 99%

Section: Kel-8 Is a Substrate Receptor For Cdl3mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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KEL-8 Is a Substrate Receptor for CUL3-dependent Ubiquitin Ligase That Regulates Synaptic Glutamate Receptor Turnover

Schaefer

Rongo

2006

MBoC

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“…VHL and SOCS proteins, via their additional protein-protein interaction modules, target various substrates differentially to the CUL2-ROC1 or CUL5-ROC2 catalytic cores (Kamura et al 1998(Kamura et al , 2001(Kamura et al , 2004Stebbins et al 1999;Zhang et al 1999). Omitting a linker, CUL3 utilizes its N-terminal domain to bind to proteins with a conserved 100-residue protein motif known as a BTB domain, which, via additional protein-protein interaction domains, then target various substrates to the CUL3-ROC1 catalytic core (Furukawa et al 2003;Geyer et al 2003;Pintard et al 2003;Xu et al 2003). The presence of multiple substrate receptors-mammals express >60 F-box, 40 SOCS, and 200 BTB proteins-suggests that cullins may form the largest family of E3 ligase complexes and control the ubiquitination of a wide variety of substrates.…”

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confidence: 99%

DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4–ROC1 ubiquitin ligases

He¹,

McCall²,

et al. 2006

Genes Dev.

295

344

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Cullins assemble the largest family of ubiquitin ligases by binding with ROC1 and various substrate receptors. CUL4 function is linked with many cellular processes, but its substrate-recruiting mechanism remains elusive. We identified a protein motif, the DWD box (DDB1-binding WD40 protein), and demonstrated the binding of 15 DWD proteins with DDB1-CUL4A. We provide evidence supporting the critical function of the DWD box and DDB1's role as the linker mediating DWD protein association with CUL4A. A database search predicts that about one-third of WD40 proteins, 90 in humans, contain the DWD box, suggesting a potentially large number of DWD-DDB1-CUL4-ROC1 E3 ligases. The ubiquitin-proteasome pathway regulates the concentration and conformation of many cellular proteins in response to changes in physiological conditions. This pathway consists of a cascade of three activities performed by E1 (ubiquitin-activating), E2 (ubiquitin-conjugating), and E3 (ubiquitin ligase) enzymes (Hochstrasser 1996;King et al. 1996;Hershko and Ciechanover 1998). A critical step in this process is how individual protein substrates are recruited to specific E3 ligases. The RING family represents the major family of E3 ligases. Members either contain an intrinsic RING finger domain (as in MDM2 and BRCA1) or bind in trans with a small RING finger protein, such as ROC1 (also known as Rbx1 and Hrt1) by the cullins, to recruit and activate an E2 (Jackson et al. 2000;Petroski and Deshaies 2005).A remarkable aspect of cullin E3 ligases is that each cullin can assemble into many distinct cullin-RING-dependent ligases (CRLs) by interacting with a conserved motif present in multiple proteins (Petroski and Deshaies 2005). To recruit specific substrates, CUL1 utilizes an N-terminal domain to bind with a linker protein, SKP1 (Feldman et al. 1997;Skowyra et al. 1997;, which does not interact with other cullins (Michel and Xiong 1998). SKP1 uses a separate domain to bind with a conserved protein motif, the F box, which, via its additional protein-protein interaction modules, recruits various substrates, often phosphorylated, to the CUL1-ROC1 catalytic core. To bring specific substrates to CUL2-and CUL5-dependent ligases, a heterodimeric linker complex containing elongins B and C binds simultaneously to an analogous N-terminal domain in CUL2 and CUL5 and to two similar protein motifs, the VHL box and SOCS box. VHL and SOCS proteins, via their additional protein-protein interaction modules, target various substrates differentially to the CUL2-ROC1 or CUL5-ROC2 catalytic cores (Kamura et al. 1998(Kamura et al. , 2001(Kamura et al. , 2004Stebbins et al. 1999;Zhang et al. 1999). Omitting a linker, CUL3 utilizes its N-terminal domain to bind to proteins with a conserved 100-residue protein motif known as a BTB domain, which, via additional protein-protein interaction domains, then target various substrates to the CUL3-ROC1 catalytic core (Furukawa et al. 2003;Geyer et al. 2003;Pintard et al. 2003;Xu et al. 2003). The presence of multiple substrate receptors-...

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“…4). Thus, proteins of this group are found in lower eukaryotes, such as [29][30][31] . CUL-3 is an E2 ubiquitin conjugating enzyme.…”

Section: Btb/poz Domainsmentioning

confidence: 99%

Phylogeny of the TRAF/MATH Domain

Zapata

Martínez-García²,

Lefebvre³

Advances in Experimental Medicine and Biology

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This chapter is dedicated to the memory of José Zapata Ruiz, my beloved father and strongest supporter. TLR AbstractThe TNF-Receptor Associated Factor (TRAF) domain (TD), also known as the meprin and TRAF-C homology (MATH) domain is a fold of seven anti-parallel β-helices that participates in protein-protein interactions. This fold is broadly represented among eukaryotes, where it is found associated with a discrete set of protein-domains. Virtually all protein families encompassing a TRAF/MATH domain seem to be involved in the regulation of protein processing and ubiquitination, strongly suggesting a parallel evolution of the TRAF/MATH domain and certain proteolysis pathways in eukaryotes.The restricted number of living organisms for which we have information of their genetic and protein make-up limits the scope and analysis of the MATH domain in evolution. However, the available information allows us to get a glimpse on the origins, distribution and evolution of the TRAF/MATH domain, which will be overviewed in this chapter.Introduction.

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BTB/POZ Domain Proteins Are Putative Substrate Adaptors for Cullin 3 Ubiquitin Ligases

Cited by 301 publications

References 35 publications

KEL-8 Is a Substrate Receptor for CUL3-dependent Ubiquitin Ligase That Regulates Synaptic Glutamate Receptor Turnover

KEL-8 Is a Substrate Receptor for CUL3-dependent Ubiquitin Ligase That Regulates Synaptic Glutamate Receptor Turnover

DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4–ROC1 ubiquitin ligases

Phylogeny of the TRAF/MATH Domain

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