Proteasome-Mediated Degradation of p21 via N-Terminal Ubiquitinylation

  title={Proteasome-Mediated Degradation of p21 via N-Terminal Ubiquitinylation},
  author={Joanna Bloom and Virginia Amador and Francesca Bartolini and George N Demartino and Michele Pagano},

Figures from this paper

N-Terminal Ubiquitination of Extracellular Signal-Regulated Kinase 3 and p21 Directs Their Degradation by the Proteasome

It is shown that a lysineless mutant of ERK3 is still ubiquitinated in vivo and requires a functional ubiquitin conjugation pathway for its degradation, and suggests that N-terminal ubiquitination is a more prevalent modification than originally recognized.

Ubiquitin-independent degradation: lessons from the p53 model.

The discovery that native p53 is also prone to ubiquitin-independent 20S proteasomal degradation, suggesting that certain proteins are inherently unstable, suggests the existence of ubiquitIn-independent mechanisms for proteasome protein degradation in the cells.

N-terminal polyubiquitination and degradation of the Arf tumor suppressor.

Kinetic metabolic labeling of cells with [3H]-leucine indicated that p19 Arf is a relatively stable protein whose degradation depends upon the ubiquitin-proteasome pathway, and re-engineering of the p19Arf N terminus to provide consensus sequences for N-acetylation limited Arf ubiquitination and decelerated its turnover.

p53 Proteasomal Degradation: Poly-Ubiquitination is Not the Whole Story

It is suggested that p53 also undergoes ubiquitin-independent degradation by the 20S proteasomes and that this process is regulated by NAD(P)H quinone oxidoreductase 1 (NQO1) together with NADH.

A 20S proteasome receptor for degradation of intrinsically disordered proteins

A model whereby the PSMA3 C-terminal region plays a role of substrate receptor in the process of proteasomal degradation of many IDPs is proposed, whereby this fragment in isolation blocks the degradation of a large number of IDPs in vitro and increases the half-life of proteins in vivo.

Ubiquitin-dependent Degradation of p73 Is Inhibited by PML

It is found that p300-mediated acetylation of p73 protects it against ubiquitinylation and that PML regulates p73 stability by positively modulating its acetylated levels, thus providing further insights on the molecular network for tumor suppression.

N-terminal ubiquitination: more protein substrates join in.




In vivo ubiquitination and proteasome-mediated degradation of p53(1).

In this study, inhibitors of the 26S proteasome have been used to further explore the role of ubiquitin proteolysis in regulating p53 turnover and indicate that ubiquitIn-p53 conjugates were detected in untreated as well as gamma-irradiated cells, indicating that Ubiquitin-dependent proteolytic plays a role in the normal turnover of p53.

A novel site for ubiquitination: the N‐terminal residue, and not internal lysines of MyoD, is essential for conjugation and degradation of the protein

The data suggest that conjugation of MyoD occurs via a novel modification involving attachment of ubiquitin to the N‐terminal residue, which is sufficient and necessary for promotion of conjugations and subsequent degradation of the protein.

SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27

It is shown that the F-box protein SKP2 specifically recognizes p27 in a phosphorylation-dependent manner that is characteristic of an F- box-protein–substrate interaction and is subject to dual control by the accumulation of bothSKP2 and cyclins following mitogenic stimulation.

Ubiquitinylation is not an absolute requirement for degradation of c- Jun protein by the 26 S proteasome

Using cell-free degradation assays, it is shown that ubiquitinylation, along with other types of tagging, is not an absolute prerequisite for ATP-dependent degradation of c-Jun by the 26 S proteasome, indicating that a protein may bear intrinsic structural determinants allowing its selective recognition and breakdown by the26 S proteAsome.

Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation.

It is demonstrated that p27 ubiquitination (as assayed in vivo and in an in vitro reconstituted system) is cell-cycle regulated and that Cdk activity is required for the in vitro ubiquitinations of p27.

Role of the SCFSkp2 Ubiquitin Ligase in the Degradation of p21Cip1 in S Phase*

It is shown that p21 is a good substrate for an SCF (Skp1-Cullin1-F-boxprotein) ubiquitin ligase complex, which contains the F-box protein Skp2 (S phase kinase-associated protein 2) and the accessory protein Cks1 (cyclin kinase subunit 1).

Degradation of the Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) by the Ubiquitin-Proteasome Pathway

It is shown that LMP1 is a substrate of the ubiquitin pathway and is ubiquitinated both in vitro and in vivo, and suggested that phosphorylation is also required for degradation of L MP1.