ArticleCell cycle (Georgetown, Tex.)2012
Orc2 protects ORCA from ubiquitin-mediated degradation.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Polycomb-mediated 3D-genome organization controls replication timing.Science advances · 2026Article
- Review
- A dual role for the chromatin reader ORCA/LRWD1 in targeting the origin recognition complex to chromatin.The EMBO journal · 2023Article
- ORChestra coordinates the replication and repair music.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- The E3 ligase RFWD3 stabilizes ORC in a p53-dependent manner.Cell cycle (Georgetown, Tex.) · 2020Article
- The emerging role for Cullin 4 family of E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Review
- Nonreplicative functions of the origin recognition complex.Nucleus (Austin, Tex.) · 2018Review
- Chromatin-Bound Cullin-Ring Ligases: Regulatory Roles in DNA Replication and Potential Targeting for Cancer Therapy.Frontiers in molecular biosciences · 2018Review
- Quantitative phosphoproteome on the silkworm (Bombyx mori) cells infected with baculovirus.Virology journal · 2017Article
- Review
- Article
- Cellular senescence and protein degradation: breaking down cancer.Cell cycle (Georgetown, Tex.) · 2014Article
- ORCA is regulated by ubiquitin-mediated degradation to control Orc2 function.Cell cycle (Georgetown, Tex.) · 2012Article
- Flipping the switch from g1 to s phase with e3 ubiquitin ligases.Genes & cancer · 2012Article
- Emerging players in the initiation of eukaryotic DNA replication.Cell division · 2012Article
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2 authors at 2 institutions in 1 country.
Funding
Abstract
Origin recognition complex (ORC) is highly dynamic, with several ORC subunits getting posttranslationally modified by phosphorylation or ubiquitination in a cell cycle-dependent manner. We have previously demonstrated that a WD repeat containing protein ORC-associated (ORCA/LRWD1) stabilizes the ORC on chromatin and facilitates pre-RC assembly. Further, ORCA levels are cell cycle-regulated, with highest levels during G(1), and progressively decreasing during S phase, but the mechanism remains to be elucidated. We now demonstrate that ORCA is polyubiquitinated in vivo, with elevated ubiquitination observed at the G(1)/S boundary. ORCA utilizes lysine-48 (K48) ubiquitin linkage, suggesting that ORCA ubiquitination mediates its regulated degradation. Ubiquitinated ORCA is re-localized in the form of nuclear aggregates and is predominantly associated with chromatin. We demonstrate that ORCA associates with the E3 ubiquitin ligase Cul4A-Ddb1. ORCA is ubiquitinated at the WD40 repeat domain, a region that is also recognized by Orc2. Furthermore, Orc2 associates only with the non-ubiquitinated form of ORCA, and Orc2 depletion results in the proteasome-mediated destabilization of ORCA. Based on the results, we suggest that Orc2 protects ORCA from ubiquitin-mediated degradation in vivo.
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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.