The plant N‐degron pathways of ubiquitin‐mediated proteolysis

Holdsworth, Michael J.; Vicente, Jorge; Sharma, Gunjan; Abbas, Mohamad; Zubrycka, Agata

doi:10.1111/jipb.12882

Cited by 64 publications

(62 citation statements)

References 115 publications

(204 reference statements)

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“…We focus particularly on the pathways discovered in the past few years, and direct readers to excellent reviews that provide more comprehensive coverage of the Arg/N-degron [ 14 , 15 ] and Ac/N-degron [ 19 ] pathways. Our scope is restricted to pathways shown to occur in human cells, although N-degron pathways are also known to play important roles in plants [ 20–22 ] and bacteria [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Tying up loose ends: the N-degron and C-degron pathways of protein degradation

Timms

Koren

2020

Biochemical Society Transactions

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Selective protein degradation by the ubiquitin-proteasome system (UPS) is thought to be governed primarily by the recognition of specific motifs — degrons — present in substrate proteins. The ends of proteins — the N- and C-termini – have unique properties, and an important subset of protein–protein interactions involve the recognition of free termini. The first degrons to be discovered were located at the extreme N-terminus of proteins, a finding which initiated the study of the N-degron (formerly N-end rule) pathways, but only in the last few years has it emerged that a diverse set of C-degron pathways target analogous degron motifs located at the extreme C-terminus of proteins. In this minireview we summarise the N-degron and C-degron pathways currently known to operate in human cells, focussing primarily on those that have been discovered in recent years. In each case we describe the cellular machinery responsible for terminal degron recognition, and then consider some of the functional roles of terminal degron pathways. Altogether, a broad spectrum of E3 ubiquitin ligases mediate the recognition of a diverse array of terminal degron motifs; these degradative pathways have the potential to influence a wide variety of cellular functions.

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Section: Introductionmentioning

confidence: 99%

Tying up loose ends: the N-degron and C-degron pathways of protein degradation

Timms

Koren

2020

Biochemical Society Transactions

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“…To search for integrators of variable oxygen concentrations into developmental programmes, recent studies have been directed to oxygen‐dependent substrates of the Arg/N‐degron pathway (Varshavsky, 2019). Since several reviews have been written to discuss the N‐degron and C‐degron pathways for protein degradation, our discussion will be brief (Dissmeyer, 2019; Holdsworth et al , 2019; Varshavsky, 2019). These biochemical pathways determine protein half‐life on the basis of the amino acid residues exposed at the N‐ and C‐termini (Bachmair et al , 1986; Koren et al , 2018; Lin et al , 2018).…”

Section: Molecular Mechanisms Involved In Oxygen‐dependent Developmentmentioning

confidence: 99%

Molecular oxygen as a signaling component in plant development

2020

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While traditionally hypoxia has been studied as a detrimental component of flooding stress, the last decade has flourished with studies reporting the involvement of molecular oxygen availability in plant developmental processes. Moreover, proliferating and undifferentiated cells from different plant tissues were found to reside in endogenously generated hypoxic niches. Thus, stress-associated acute hypoxia may be distinguished from constitutively generated chronic hypoxia. The Cys/Arg branch of the N-degron pathway assumes a central role in integrating oxygen levels resulting in proteolysis of transcriptional regulators that control different aspects of plant growth and development. As a target of this pathway, group VII of the Ethylene Response Factor (ERF-VII) family has emerged as a hub for the integration of oxygen dynamics in root development and during seedling establishment. Additionally, vegetative shoot meristem activity and reproductive transition were recently associated with oxygen availability via two novel substrates of the N-degron pathways: VERNALISATION 2 (VRN2) and LITTLE ZIPPER 2 (ZPR2). Together, these observations support roles for molecular oxygen as a signalling molecule in plant development, as well as in essential metabolic reactions. Here, we review recent findings regarding oxygen-regulated development, and discuss outstanding questions that spring from these discoveries.

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“…The indicated yeast strains were constructed as described in SI Appendix, Materials and Methods and Fig. S10, through factors of plants results in degradation of these proteins by the Arg/N-degron pathway (2,44,73,74,100,101). This pathway is thus a sensor of oxygen and NO and regulator of responses to these compounds (2, 100).…”

Section: Engineered Yeast Strains That Coexpress Human Proteins: Hsate1mentioning

confidence: 99%

Five enzymes of the Arg/N-degron pathway form a targeting complex: The concept of superchanneling

Hyun

Chen

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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The Arg/N-degron pathway targets proteins for degradation by recognizing their N-terminal (Nt) residues. If a substrate bears, for example, Nt-Asn, its targeting involves deamidation of Nt-Asn, arginylation of resulting Nt-Asp, binding of resulting (conjugated) Nt-Arg to the UBR1-RAD6 E3-E2 ubiquitin ligase, ligase-mediated synthesis of a substrate-linked polyubiquitin chain, its capture by the proteasome, and substrate’s degradation. We discovered that the human Nt-Asn–specific Nt-amidase NTAN1, Nt-Gln–specific Nt-amidase NTAQ1, arginyltransferase ATE1, and the ubiquitin ligase UBR1-UBE2A/B (or UBR2-UBE2A/B) form a complex in which NTAN1 Nt-amidase binds to NTAQ1, ATE1, and UBR1/UBR2. In addition, NTAQ1 Nt-amidase and ATE1 arginyltransferase also bind to UBR1/UBR2. In the yeast Saccharomyces cerevisiae, the Nt-amidase, arginyltransferase, and the double-E3 ubiquitin ligase UBR1-RAD6/UFD4-UBC4/5 are shown to form an analogous targeting complex. These complexes may enable substrate channeling, in which a substrate bearing, for example, Nt-Asn, would be captured by a complex-bound Nt-amidase, followed by sequential Nt modifications of the substrate and its polyubiquitylation at an internal Lys residue without substrate’s dissociation into the bulk solution. At least in yeast, the UBR1/UFD4 ubiquitin ligase interacts with the 26S proteasome, suggesting an even larger Arg/N-degron–targeting complex that contains the proteasome as well. In addition, specific features of protein-sized Arg/N-degron substrates, including their partly sequential and partly nonsequential enzymatic modifications, led us to a verifiable concept termed “superchanneling.” In superchanneling, the synthesis of a substrate-linked poly-Ub chain can occur not only after a substrate’s sequential Nt modifications, but also before them, through a skipping of either some or all of these modifications within a targeting complex.

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The plant N‐degron pathways of ubiquitin‐mediated proteolysis

Cited by 64 publications

References 115 publications

Tying up loose ends: the N-degron and C-degron pathways of protein degradation

Tying up loose ends: the N-degron and C-degron pathways of protein degradation

Molecular oxygen as a signaling component in plant development

Five enzymes of the Arg/N-degron pathway form a targeting complex: The concept of superchanneling

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