ArticleMolecular and cellular biology2006
Cul4A and DDB1 associate with Skp2 to target p27Kip1 for proteolysis involving the COP9 signalosome.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 102 citations in OpenAlex.
- Targeted O-GlcNAcylation of CK2α Triggers Its Ubiquitin-Proteasome Degradation and Alters Downstream Phosphorylation.ACS chemical biology · 2025Article
- Regulation of p27 (Kip1) by Ubiquitin E3 Ligase RNF6.Pharmaceutics · 2022Article
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- The splicing factor XAB2 interacts with ERCC1-XPF and XPG for R-loop processing.Nature communications · 2021Article
- CRL4AOncogene · 2021Article
- CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma.Cancer biology & medicine · 2020Article
- YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators.PLoS biology · 2020Article
- Overexpression of Cullin4A correlates with a poor prognosis and tumor progression in esophageal squamous cell carcinoma.International journal of clinical oncology · 2020Article
- Preclinical studies reveal MLN4924 is a promising new retinoblastoma therapy.Cell death discovery · 2020Article
- ZNF703 is Overexpressed in Papillary Thyroid Carcinoma Tissues and Mediates K1 Cell Proliferation.Pathology oncology research : POR · 2020Article
- Cullin Ring Ubiquitin Ligases (CRLs) in Cancer: Responses to Ionizing Radiation (IR) Treatment.Frontiers in physiology · 2019Review
- Corrected and Republished from: The COP9 Signalosome Interacts with and Regulates Interferon Regulatory Factor 5 Protein Stability.Molecular and cellular biology · 2018Article
- Breaking Bad: How Viruses Subvert the Cell Cycle.Frontiers in cellular and infection microbiology · 2018Review
- miR-181a-2 downregulates the E3 ubiquitin ligase CUL4A transcript and promotes cell proliferation.Medical oncology (Northwood, London, England) · 2017Article
- MYC Modulation around the CDK2/p27/SKP2 Axis.Genes · 2017Review
- CUL4A overexpression as an independent adverse prognosticator in intrahepatic cholangiocarcinoma.BMC cancer · 2017Article
- Article
- A new layer of degradation mechanism for PR-Set7/Set8 during cell cycle.Cell cycle (Georgetown, Tex.) · 2016Article
- The role and mechanism of CRL4 E3 ubiquitin ligase in cancer and its potential therapy implications.Oncotarget · 2015Review
- Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
DDB1, a subunit of the damaged-DNA binding protein DDB, has been shown to function also as an adaptor for Cul4A, a member of the cullin family of E3 ubiquitin ligase. The Cul4A-DDB1 complex remains associated with the COP9 signalosome, and that interaction is conserved from fission yeast to human. Studies with fission yeast suggested a role of the Pcu4-Ddb1-signalosome complex in the proteolysis of the replication inhibitor Spd1. Here we provide evidence that the function of replication inhibitor proteolysis is conserved in the mammalian DDB1-Cul4A-signalosome complex. We show that small interfering RNA-mediated knockdown of DDB1, CSN1 (a subunit of the signalosome), and Cul4A in mammalian cells causes an accumulation of p27Kip1. Moreover, expression of DDB1 reduces the level of p27Kip1 by increasing its decay rate. The DDB1-induced proteolysis of p27Kip1 requires signalosome and Cul4A, because DDB1 failed to increase the decay rate of p27Kip1 in cells deficient in CSN1 or Cul4A. Surprisingly, the DDB1-induced proteolysis of p27Kip1 also involves Skp2, an F-box protein that allows targeting of p27Kip1 for ubiquitination by the Skp1-Cul1-F-box complex. Moreover, we provide evidence for a physical association between Cul4A, DDB1, and Skp2. We speculate that the F-box protein Skp2, in addition to utilizing Cul1-Skp1, utilizes Cul4A-DDB1 to induce proteolysis of p27Kip1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.