The N-end rule pathway: Emerging functions and molecular principles of substrate recognition
ABSTRACT The N-end rule defines the protein-destabilizing activity of a given amino-terminal residue and its post-translational modification. Since its discovery 25 years ago, the pathway involved in the N-end rule has been thought to target only a limited set of specific substrates of the ubiquitin-proteasome system. Recent studies have provided insights into the components, substrates, functions and structural basis of substrate recognition. The N-end rule pathway is now emerging as a major cellular proteolytic system, in which the majority of proteins are born with or acquire specific N-terminal degradation determinants through protein-specific or global post-translational modifications.
- SourceAvailable from: Jorge Lozano-Juste
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- "This pathway is highly conserved in eukaryotes and plays a key role in the regulation of many growth and developmental processes, including apoptosis, cardiovascular development, DNA replication, and response to abiotic stresses (Sriram et al., 2011). There are two characterized branches of the N-end rule pathway: the Ac/N-end rule pathway, which targets proteins with N-terminally acetylated (Ac) residues, and the Arg/N-end rule, which recognizes specific unacetylated Nt residues (Sriram et al., 2011). Eukaryotic proteins are synthesized with methionine (Met) at the N terminus, but new N termini can be generated via the action of endopeptidases or by cotranslational cleavage of Nt-Met by methionine aminopeptidases (MAPs). "
ABSTRACT: Nitric oxide (NO) is an important signaling compound in prokaryotes and eukaryotes. In plants, NO regulates critical developmental transitions and stress responses. Here, we identify a mechanism for NO sensing that coordinates responses throughout development based on targeted degradation of plant-specific transcriptional regulators, the group VII ethylene response factors (ERFs). We show that the N-end rule pathway of targeted proteolysis targets these proteins for destruction in the presence of NO, and we establish them as critical regulators of diverse NO-regulated processes, including seed germination, stomatal closure, and hypocotyl elongation. Furthermore, we define the molecular mechanism for NO control of germination and crosstalk with abscisic acid (ABA) signaling through ERF-regulated expression of ABSCISIC ACID INSENSITIVE5 (ABI5). Our work demonstrates how NO sensing is integrated across multiple physiological processes by direct modulation of transcription factor stability and identifies group VII ERFs as central hubs for the perception of gaseous signals in plants.Molecular cell 01/2014; 53(3). DOI:10.1016/j.molcel.2013.12.020 · 14.46 Impact Factor
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- "to produce a destabilizing N - terminal residue in proteins : 1 ) cleavage of proteins by endopeptidases in the cytosol , 2 ) removal of signaling or transit peptides , and 3 ) removal of the first Met residue by Met amino - peptidase . The latter occurs only if the second residue of a protein is small ( Ala , Cys , Gly , Pro , Ser , Thr , Val ) ( Sriram et al . , 2011 ) . Interestingly , proteins with a Cys residue at the second posi - tion can be processed by the N - end rule pathway in mammals and plants . Such a protein can become accessible to ATE1 / 2 after oxidation of the N - terminal Cys via an unknown mechanism and subsequently can be processed by the N - end rule pathway . The oxidation of "
ABSTRACT: Like all aerobic organisms, plants require molecular oxygen for respiratory energy production. In plants, hypoxic conditions can occur during natural events (e.g., flooding), during developmental processes (e.g., seed germination), and in cells of compact tissues with high metabolic rates. Plant acclimation responses to hypoxia involve a modulation of gene expression leading to various biochemical, physiological, and morphological changes that stave off eventual anoxia. In contrast with the animal kingdom, a direct oxygen-sensing mechanism in plants has been elusive so far. However, two recent independent studies show that oxygen sensing in plants operates via posttranslational regulation of key hypoxia response transcription factors by the N-end rule pathway. The N-end rule is an evolutionarily conserved pathway for protein degradation that relates the fate of a protein with the identity of its N-terminal residues. Results from these studies demonstrate that oxygen-dependent modification and targeted proteolysis of members of the ethylene response factor group VII transcription factor family regulate hypoxia-responsive gene expression in Arabidopsis thaliana. The discovery of this plant hypoxia-sensing mechanism sets the stage for further research on plant homeostatic response to oxygen, which could be relevant to understanding plant distributions in flood-prone ecosystems and improving hypoxia tolerance of crops.The Plant Cell 12/2011; 23(12):4173-83. DOI:10.1105/tpc.111.093880 · 9.58 Impact Factor
Article: Plant cell biology: Sensing oxygenNature Reviews Molecular Cell Biology 11/2011; 12(12):770. DOI:10.1038/nrm3235 · 36.46 Impact Factor