Peptidic degron in EID1 is recognized by an SCF E3 ligase complex containing the orphan F-box protein FBXO21

EP300-interacting inhibitor of differentiation 1 (EID1) belongs to a protein family implicated in the control of transcription, differentiation, DNA repair, and chromosomal maintenance. EID1 has a very short half-life, especially in G0 cells. We discovered that EID1 contains a peptidic, modular degr...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2015-12, Vol.112 (50), p.15372-15377
Main Authors: Zhang, Cuiyan, Li, Xiaotong, Adelmant, Guillaume, Dobbins, Jessica, Geisen, Christoph, Oser, Matthew G., Wucherpfenning, Kai W., Marto, Jarrod A., Kaelin, William G.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Biological Sciences
Cell Cycle Proteins
DNA repair
F-Box Proteins - metabolism
HeLa Cells
Humans
Immunoprecipitation
Mass Spectrometry
Melanoma
Molecular Sequence Data
Nuclear Proteins - chemistry
Nuclear Proteins - metabolism
Peptides - chemistry
Peptides - metabolism
Polyubiquitin - metabolism
Protein Binding
Proteins
Proteolysis
Repressor Proteins - chemistry
Repressor Proteins - metabolism
Reproducibility of Results
Resting Phase, Cell Cycle
RNA, Small Interfering - metabolism
SKP Cullin F-Box Protein Ligases - metabolism
Tumors
Ubiquitination
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Summary:EP300-interacting inhibitor of differentiation 1 (EID1) belongs to a protein family implicated in the control of transcription, differentiation, DNA repair, and chromosomal maintenance. EID1 has a very short half-life, especially in G0 cells. We discovered that EID1 contains a peptidic, modular degron that is necessary and sufficient for its polyubiquitylation and proteasomal degradation. We found that this degron is recognized by an Skp1, Cullin, and F-box (SCF)-containing ubiquitin ligase complex that uses the F-box Only Protein 21 (FBXO21) as its substrate recognition subunit. SCFFBXO21polyubiquitylates EID1 both in vitro and in vivo and is required for the efficient degradation of EID1 in both cycling and quiescent cells. The EID1 degron partially overlaps with its retinoblastoma tumor suppressor protein-binding domain and is congruent with a previously defined melanoma-associated antigen-binding motif shared by EID family members, suggesting that binding to retinoblastoma tumor suppressor and melanoma-associated antigen family proteins could affect the polyubiquitylation and turnover of EID family members in cells.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1522006112