The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Role of the SCFSkp2 Ubiquitin Ligase in the Degradation of p21Cip1 in S Phase
Open accessAbstract
The cyclin-dependent kinase inhibitor p21Cip1 has important roles in the control of cell proliferation, differentiation, senescence, and apoptosis. It has been observed that p21 is a highly unstable protein, but the mechanisms of its degradation remained unknown. We show here that p21 is a good substrate for an SCF (Skp1-Cullin1-F-box protein) ubiquitin ligase complex, which contains the F-box protein Skp2 (S phase kinase-associated protein 2) and the accessory protein Cks1 (cyclin kinase subunit 1). A similar ubiquitin ligase complex has been previously shown to be involved in the degradation of a related cyclin-dependent kinase inhibitor, p27Kip1. The levels of Skp2 oscillate in the cell cycle, reaching a maximum in S phase. The ubiquitylation of p21 in vitro required the supplementation of all components of the SCF complex as well as of Cks1 and Cdk2-cyclin E. The protein kinase Cdk2-cyclin E acts both by the phosphorylation of p21 on Ser-130 and by the formation of a complex with p21, which is required for its presentation to the ubiquitin ligase. As opposed to the case of p27, the phosphorylation of p21 stimulates its ubiquitylation but is not absolutely required for this process. Levels of p21 are higher in Skp2-/- mouse embryo fibroblasts than in wild-type fibroblasts in the S phase, and the rates of the degradation of p21 are slower in cells that lack Skp2. It is suggested that SCFSkp2 participates in the degradation of p21 in the S phase.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
CDK inhibitors: positive and negative regulators of G1-phase progression
Sherr, C. J., & Roberts, J. M. (1999) · Genes & Development · doi:10.1101/gad.13.12.1501 · Cited by 6,115
Inhibitors of mammalian G1 cyclin-dependent kinases.
Sherr, C. J., & Roberts, J. M. (1995) · Genes & Development · doi:10.1101/gad.9.10.1149 · Cited by 3,243
The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA
Waga, S., Hannon, G. J., Beach, D., & Stillman, B. (1994) · Nature · doi:10.1038/369574a0 · Cited by 1,655
SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27
Carrano, A. C., Eytan, E., Hershko, A., & Pagano, M. (1999) · Nature Cell Biology · doi:10.1038/12013 · Cited by 1,543
Self-citationStructure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex
Zheng, N., Schulman, B. A., Song, L., Miller, J. J., Jeffrey, P. D., Wang, P., Chu, C., Koepp, D. M., Elledge, S. J., Pagano, M., et al. (2002) · Nature · doi:10.1038/416703a · Cited by 1,507
Self-citationSCF and Cullin/RING H2-Based Ubiquitin Ligases
Deshaies, R. J. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.435 · Cited by 1,242
Cyclin E-CDK2 is a regulator of p27Kip1.
Sheaff, R. J., Groudine, M., Gordon, M., Roberts, J. M., & Clurman, B. E. (1997) · Genes & Development · doi:10.1101/gad.11.11.1464 · Cited by 911
Tsvetkov, L. M., Yeh, K.-H., Lee, S.-J., Sun, H., & Zhang, H. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80290-5 · Cited by 791
Nakayama, K. (2000) · The EMBO Journal · doi:10.1093/emboj/19.9.2069 · Cited by 717
Self-citationp45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells
Sutterlüty, H., Chatelain, E., Marti, A., Wirbelauer, C., Senften, M., Müller, U., & Krek, W. (1999) · Nature Cell Biology · doi:10.1038/12027 · Cited by 700
Cited by
p21 in cancer: Intricate networks and multiple activities
Abbas, T., & Dutta, A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2657 · Cited by 2,712
The SCF ubiquitin ligase: insights into a molecular machine
Cardozo, T., & Pagano, M. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1471 · Cited by 1,114
Self-citationDeregulated proteolysis by the F-box proteins SKP2 and β-TrCP: tipping the scales of cancer
Frescas, D., & Pagano, M. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2396 · Cited by 890
Self-citationCyclin D1, cancer progression, and opportunities in cancer treatment
Qie, S., & Diehl, J. A. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1475-3 · Cited by 657
Wang, I.-C., Chen, Y.-J., Hughes, D., Petrovic, V., Major, M. L., Park, H. J., Tan, Y., Ackerson, T., & Costa, R. H. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.10875-10894.2005 · Cited by 627
Metadata
- Authors
- Bornstein, G., Bloom, J., Sitry-Shevah, D., Nakayama, K., Pagano, M., & Hershko, A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-07
- Volume
- 278
- Issue
- 28
- Pages
- 25752-25757
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2102951681
- Cited by
- 494
- References
- 39
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Role of the SCFSkp2 Ubiquitin Ligase in the Degradation of p21Cip1 in S Phase. https://app.cochat.ai/papers/10.1074/jbc.m301774200
- The paper
- Bornstein, G., Bloom, J., Sitry-Shevah, D., Nakayama, K., Pagano, M., & Hershko, A. (2003). Role of the SCFSkp2 Ubiquitin Ligase in the Degradation of p21Cip1 in S Phase. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m301774200
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
