Ubiquitin Specific Peptidase 8 Proteine (USP8)

Human Ubiquitin Specific Peptidase 8 (USP8) Interaktionspartner

1. Deubiquitination of EPG5 by USP8 guards the autophagic flux in embryonic stem cells (ESCs) to maintain their stemness. This work uncovers a novel crosstalk pathway between ubiquitination and autophagy through USP8-EPG5 interaction to regulate the stemness of ESCs.

2. USP8 interacted with transforming growth factorbetaactivated kinase1 (TAK1) and deubiquitinated the K63linked ubiquitination of TAK1.

3. SFN enhances RTK stabilization through abnormal USP8 regulation in lung adenocarcinoma

4. Biophysical and structural insight into the USP8/14-3-3 interaction.

5. High USP8 expression is associated with breast neoplasms.

6. High expression of USP8 was correlated with advanced tumor stage and high recurrence risk. Moreover, USP8 was identified as a novel independent prognostic factor for CSCC patients.

7. In summary, we show that, contrary to the pituitary ACTH-secreting tumors, the USP8 hotspot sequence on exon 14 is not mutated in tumors causing ectopic ACTH secretion syndrome (EAS). Although USP8 is expressed in all EAS tumors examined, our in vitro data indicate that it is not involved in the regulation of ectopic proopiomelanocortin transcription.

8. USP8 deubiquitinates Sec31A and inhibits the formation of large COPII carriers, thereby suppressing collagen IV secretion.

9. review: role of USP8 driver mutations in Cushing's Disease

10. Data (including data from studies using knockout and transgenic mice/cells) suggest that CLEC16A, NRDP1, and USP8 form tripartite complex; CLEC16A-NRDP1-USP8 complex appears to rely on ubiquitin signals to promote mitophagy and maintain mitochondrial function necessary for beta-cell function. (CLEC16A = C-type lectin domain family 16 member A; NRDP1 = ubiquitin-protein ligase NRDP1; USP8 = ubiquitin specific peptidase 8)

11. the EGFR-USP8-trichoplein-Aurora A axis is a critical signaling cascade that restricts ciliogenesis in dividing cells, and functions to facilitate cell proliferation

12. in human cells, Usp8 knockdown increased the lysosomal degradation of alpha-synuclein.

13. Overexpression of USP8 in lung adenocarcinoma is an early event during the course of tumor progression, and is related to EGFR expression.

14. Somatic mutations in USP8 are common in Nelson's tumors, and are associated with less favorable outcome after surgery.

15. Data indicate that USP8 functions as a novel deubiquitylase of FLIPL and inhibits extrinsic apoptosis by stabilizing FLIPL.

16. Somatic USP8 gene mutations are a common cause of pediatric Cushing disease due to pituitary adenoma.

17. findings demonstrate that USP8 plays a key role in the trafficking and degradation of BACE1 by deubiquitinating lysine 501.

18. USP8 regulates VEGFR2 trafficking, signaling and proteolysis.

19. Ubpy loss of function results in the accumulation of autophagosomes due to a blockade of the autophagy flux.

20. Results show that in addition to the scaffolding function in complex formation, BRUCE has an E3 ligase function to promote BRIT1 deubiquitination by USP8 leading to accumulation of BRIT1 at DNA double-strand break.

Mouse (Murine) Ubiquitin Specific Peptidase 8 (USP8) Interaktionspartner

1. Deubiquitination of EPG5 by USP8 guards the autophagic flux in embryonic stem cells (ESCs) to maintain their stemness. This work uncovers a novel crosstalk pathway between ubiquitination and autophagy through USP8-EPG5 interaction to regulate the stemness of ESCs.

2. USP8 interacted with transforming growth factorbetaactivated kinase1 (TAK1) and deubiquitinated the K63linked ubiquitination of TAK1.

3. UBPy-sorted cargo to acrosome biogenesis and effects of its derailment in a mouse model of globozoospermia, the infertile Vps54 (L967Q) mutant, are reported.

4. the membrane receptor MET, described herein for the first time in spermatids, is a USP8/UBPy-target substrate is delivered to the acrosome.

5. in neuronal cells USP8 could be involved in endosomal trafficking, retrograde transport and synaptic plasticity. In disorders leading to neurodegeneration USP8 is upregulated and could influence the neuron-oligodendrocyte interactions.

6. The spatio-temporal expression of mUBPy suggests that the enzyme may be involved in neuroregulatory processes during embryogenesis.

7. a role for the USP8.STAM complex as a protective mechanism regulating early endosomal sorting of EGFR between pathways destined for lysosomal degradation and recycling.

8. USP8 was able to interact with spermatid endosomal-sorting complex required for transport-0 and microtubule structures; USP8 can directly link, via its MIT domain, the labeled vesicles/developing acrosome to microtubules.

9. in wobbler testis expression of mouse ubiquitin-specific processing protease (mUBPy)is up-regulated, while a differential sorting of the protein characterizes wobbler spermatids where acrosome formation is impaired

10. Data indicate a novel mechanism where diacylglycerol kinase delta and protein kinase Calpha modulate the levels of ubiquitinated epidermal growth factor receptors through Akt and ubiquitin-specific protease 8.

11. deubiquitinating enzyme specifically expressed in testis, associates with the acrosome and centrosome in mouse germ cells

12. Results indicate that Nrdp1 is a specific target for the USP8 deubiquitinating enzyme and are consistent with a model where USP8 augments Nrdp1 activity by mediating its stabilization.

13. We conclude that UBPY negatively regulates the rate of EGFR down-regulation by deubiquitinating EGFR on endosomes.

14. UBPY-mediated EGFR de-ubiquitination promotes EGFR degradation

15. UBPy may play a key role during mouse fertilization as a novel centrosomal component.

16. These results unveil a central and nonredundant role of UBPy in growth regulation, endosomal sorting, and the control of receptor tyrosine kinases in vivo.

17. UBPY is catalytically inhibited in a phosphorylation-dependent manner by 14-3-3s during the interphase, and this regulation is cancelled in the M phase.

18. Moderate expression of mouse UBPy was found in the amygdaloid complex, supraoptic nucleus, arcuate and ventromedial nuclei of hypothalamus, lateral hypothalamic area and lateral and reticular part of the substantia nigra.