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PMID:19424180

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Citation

Berthouze, M, Venkataramanan, V, Li, Y and Shenoy, SK (2009) The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization. EMBO J. 28:1684-96

Abstract

Agonist-induced ubiquitination of the beta(2) adrenergic receptor (beta(2)AR) functions as an important post-translational modification to sort internalized receptors to the lysosomes for degradation. We now show that this ubiquitination is reversed by two deubiquitinating enzymes, ubiquitin-specific proteases (USPs) 20 and 33, thus, inhibiting lysosomal trafficking when concomitantly promoting receptor recycling from the late-endosomal compartments as well as resensitization of recycled receptors at the cell surface. Dissociation of constitutively bound endogenously expressed USPs 20 and 33 from the beta(2)AR immediately after agonist stimulation and reassociation on prolonged agonist treatment allows receptors to first become ubiquitinated and then deubiquitinated, thus, providing a 'trip switch' between degradative and recycling pathways at the late-endosomal compartments. Thus, USPs 20 and 33 serve as novel regulators that dictate both post-endocytic sorting as well as the intensity and extent of beta(2)AR signalling from the cell surface.

Links

PubMed PMC2699358 Online version:10.1038/emboj.2009.128

Keywords

Adrenergic beta-2 Receptor Agonists; Animals; Arrestins/metabolism; Catalytic Domain; Cattle; Cell Compartmentation; Endocytosis; Endosomes/enzymology; Enzyme Activation; Gene Knockdown Techniques; Humans; Lysosomes/enzymology; Mutant Proteins/metabolism; Protein Binding; Protein Processing, Post-Translational; Protein Transport; Rats; Receptors, Adrenergic, beta-2/metabolism; Ubiquitin Thiolesterase/metabolism; Ubiquitination

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ADRB2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9Y2K6

F

Seeded From UniProt

complete

HUMAN:ADRB2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8TEY7

F

Seeded From UniProt

complete

HUMAN:UBP20

involved_in

GO:0016579: protein deubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBP20

involved_in

GO:0008277: regulation of G protein-coupled receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBP20

enables

GO:0004197: cysteine-type endopeptidase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:UBP20

enables

GO:0004843: thiol-dependent deubiquitinase

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:UBP20

enables

GO:0001664: G protein-coupled receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P07550

F

Seeded From UniProt

complete

HUMAN:UBP20

involved_in

GO:0071108: protein K48-linked deubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBP20

involved_in

GO:0070536: protein K63-linked deubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBP33

enables

GO:0001664: G protein-coupled receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P07550

F

Seeded From UniProt

complete

HUMAN:UBP33

enables

GO:0004197: cysteine-type endopeptidase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:UBP33

enables

GO:0036459: thiol-dependent ubiquitinyl hydrolase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:UBP33

involved_in

GO:0008277: regulation of G protein-coupled receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBP33

involved_in

GO:0016579: protein deubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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