UBXN7 docks on neddylated cullin complexes using its UIM motif and causes HIF1α accumulation

Bandau, Susanne; Knebel, Axel; Gage, Zoe Olivia; Wood, Nicola T.; Alexandru, Gabriela

doi:10.1186/1741-7007-10-36

Cited by 57 publications

(85 citation statements)

References 52 publications

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“…Such synergies can be caused by simultaneously disrupting two components of a protein complex (Pérez-Pérez et al, 2009;Lanctot et al, 2013). In addition, ubiquitin receptors have been reported to interact with E3 ubiquitin ligases and influence the degradation of their ubiquitinated substrates in animals (Alexandru et al, 2008;Bandau et al, 2012). We therefore assessed whether DA1 interacts with the E3 ubiquitin ligase DA2 using an in vitro interaction/ pull-down experiment.…”

Section: Da1 Interacts With Da2 In Vitro and In Vivomentioning

confidence: 99%

The Ubiquitin Receptor DA1 Interacts with the E3 Ubiquitin Ligase DA2 to Regulate Seed and Organ Size in Arabidopsis

et al. 2013

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ORCID ID: 0000-0002-0025-4444 (Y.L.).Seed size in higher plants is determined by the coordinated growth of the embryo, endosperm, and maternal tissue. Several factors that act maternally to regulate seed size have been identified, such as AUXIN RESPONSE FACTOR2, APETALA2, KLUH, and DA1, but the genetic and molecular mechanisms of these factors in seed size control are almost totally unknown. We previously demonstrated that the ubiquitin receptor DA1 acts synergistically with the E3 ubiquitin ligase ENHANCER1 OF DA1 (EOD1)/BIG BROTHER to regulate the final size of seeds in Arabidopsis thaliana. Here, we describe another RING-type protein with E3 ubiquitin ligase activity, encoded by DA2, which regulates seed size by restricting cell proliferation in the maternal integuments of developing seeds. The da2-1 mutant forms large seeds, while overexpression of DA2 decreases seed size of wild-type plants. Overexpression of rice (Oryza sativa) GRAIN WIDTH AND WEIGHT2, a homolog of DA2, restricts seed growth in Arabidopsis. Genetic analyses show that DA2 functions synergistically with DA1 to regulate seed size, but does so independently of EOD1. Further results reveal that DA2 interacts physically with DA1 in vitro and in vivo. Therefore, our findings define the genetic and molecular mechanisms of three ubiquitin-related proteins DA1, DA2, and EOD1 in seed size control and indicate that they are promising targets for crop improvement.

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Section: Da1 Interacts With Da2 In Vitro and In Vivomentioning

confidence: 99%

The Ubiquitin Receptor DA1 Interacts with the E3 Ubiquitin Ligase DA2 to Regulate Seed and Organ Size in Arabidopsis

et al. 2013

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“…A study has identified hundreds of potential CRL targets, where functional inactivation of cullins was combined with genetic and proteomic approaches, displaying the diversity of CRLs to control protein stability (Emanuele et al 2011). Different models exist for the role of NEDD8 in the regulation of CRL function, including cullin dimerisation, dissociation of cullins from its negative regulator CAND1, conformational changes that bring the E3-RING ligases RBX1/2 in close proximity to the substrate protein, stabilisation of the active CRL state, or control the CRL binding with other E3-ligases and components of the p97 pathway (Duda et al 2008, Saha & Deshaies 2008, Merlet et al 2009, Deshaies et al 2010, Duda et al 2011, Bandau et al 2012, den Besten et al 2012, Kelsall et al 2013, Pierce et al 2013, Wu et al 2013, Zemla et al 2013.…”

Section: Substrates For Nedd8mentioning

confidence: 99%

Regulation of cancer-related pathways by protein NEDDylation and strategies for the use of NEDD8 inhibitors in the clinic

Abidi

Xirodimas

2014

Endocrine-Related Cancer

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Post-translational modification of proteins with ubiquitin and ubiquitin-like molecules (UBLs) controls a vast if not every biological process in the cell. It is not surprising that deregulation in ubiquitin and UBL signalling has been implicated in the pathogenesis of many diseases and that these pathways are considered as major targets for therapeutic intervention. In this review, we summarise recent advances in our understanding of the role of the UBL neural precursor cell expressed developmentally downregulated-8 (NEDD8) in cancer-related processes and potential strategies for the use of NEDD8 inhibitors as chemotherapeutics.

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“…Among these receptors, the UIM domain of Rpn10 has been most studied and is believed to bind Ub chains directly (56). Moreover, the UIM domain of another protein, UBXD7, has been shown to bind to conjugated Nedd8 on CUL2 (94,95). This inspired us to examine whether Rub1 and the Rub1-Ub heterodimer interact with the UIM domain of Rpn10.…”

Section: Rub1-ub Heterodimer Is Recognized By the Proteasome And Procmentioning

confidence: 99%

Recognition and Cleavage of Related to Ubiquitin 1 (Rub1) and Rub1-Ubiquitin Chains by Components of the Ubiquitin-Proteasome System

Singh

Zerath

Kleifeld

et al. 2012

Molecular & Cellular Proteomics

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Of all ubiquitin-like proteins, Rub1 (Nedd8 in mammals) is the closest kin of ubiquitin. We show via NMR that structurally, Rub1 and ubiquitin are fundamentally similar as well. Despite these profound similarities, the prevalence of Rub1/Nedd8 and of ubiquitin as modifiers of the proteome is starkly different, and their attachments to specific substrates perform different functions. Recently, some proteins, including p53, p73, EGFR, caspase-7, and Parkin, have been shown to be modified by both Rub1/ Nedd8 and ubiquitin within cells. To understand whether and how it might be possible to distinguish among the same target protein modified by Rub1 or ubiquitin or both, we examined whether ubiquitin receptors can differentiate between Rub1 and ubiquitin. Surprisingly, Rub1 interacts with proteasome ubiquitin-shuttle proteins comparably to ubiquitin but binds more weakly to a proteasomal ubiquitin receptor Rpn10. We identified Rub1-ubiquitin heteromers in yeast and Nedd8-Ub heteromers in human cells. We validate that in human cells and in vitro, human Rub1 (Nedd8) forms chains with ubiquitin where it acts as a chain terminator. Interestingly, enzymatically assembled K48-linked Rub1-ubiquitin heterodimers are recognized by various proteasomal ubiquitin shuttles and receptors comparably to K48-linked ubiquitin homodimers. Furthermore, these heterologous chains are cleaved by COP9 signalosome or 26S proteasome. A derubylation function of the proteasome expands the repertoire of its enzymatic activities. In contrast, Rub1 conjugates may be somewhat resilient to the actions of other canonical deubiquitinating enzymes. Taken together, these findings suggest that once Rub1/Nedd8 is channeled into ubiquitin pathways, it is recognized essentially like The selective degradation of many proteins in eukaryotic cells is a highly specific and irreversible process required to perform vital cellular functions such as cell cycle progression (1, 2), differentiation and development (3, 4), and transcriptional control (5). One of the major pathways involved in this selective degradation is the ubiquitin-proteasome pathway. In this pathway, ubiquitin (Ub), a 76-amino-acid protein, is attached to the substrate, and this is followed by the recognition and degradation of the substrate by a protein complex collectively known as proteasome (6 -8).The attachment of Ub (ubiquitination) to a substrate protein is achieved via a cascade of enzymatic reactions (involving E1, E2, and E3 enzymes) that results in the formation of an isopeptide bond between the C-terminal glycine of Ub and a lysine residue of the substrate (9 -11). Sequential repetition of this cascade can result in the attachment of a chain of Ub molecules (polyubiquitin) to the substrate protein. The length and topology of the polyubiquitin (polyUb) tag decide the fate of the substrate protein. For example, we and others have shown that a K48-linked tetraubiquitin (tetraUb) chain that acts as a proteasomal degradation signal forms a "closed" structure (12, 13), whereas a K63-linked Ub...

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UBXN7 docks on neddylated cullin complexes using its UIM motif and causes HIF1α accumulation

Cited by 57 publications

References 52 publications

The Ubiquitin Receptor DA1 Interacts with the E3 Ubiquitin Ligase DA2 to Regulate Seed and Organ Size in Arabidopsis

The Ubiquitin Receptor DA1 Interacts with the E3 Ubiquitin Ligase DA2 to Regulate Seed and Organ Size in Arabidopsis

Regulation of cancer-related pathways by protein NEDDylation and strategies for the use of NEDD8 inhibitors in the clinic

Recognition and Cleavage of Related to Ubiquitin 1 (Rub1) and Rub1-Ubiquitin Chains by Components of the Ubiquitin-Proteasome System

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