ArticleMolecular and cellular biology2008
MDMX promotes proteasomal turnover of p21 at G1 and early S phases independently of, but in cooperation with, MDM2.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 77 citations in OpenAlex.
- Subcellular compartmentalization dependent dichotomy of p21 in cancer.Molecular biology reports · 2026Review
- MDM4 at the Crossroads: Beyond p53 and MDM2.Cancers · 2026Review
- Cellular carcinogenesis in preleukemic conditions:drivers and defenses.Fukushima journal of medical science · 2024Review
- Ubiquitin receptors play redundant roles in the proteasomal degradation of the p53 repressor MDM2.FEBS letters · 2022Article
- Contribution of MicroRNAs in Chemoresistance to Cisplatin in the Top Five Deadliest Cancer: An Updated Review.Frontiers in pharmacology · 2022Review
- MDM2, MDMX, and p73 regulate cell-cycle progression in the absence of wild-type p53.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- SNPs in miRNAs and Target Sequences: Role in Cancer and Diabetes.Frontiers in genetics · 2021Review
- Mdm4 supports DNA replication in a p53-independent fashion.Oncogene · 2020Article
- Mdm2 and MdmX RING Domains Play Distinct Roles in the Regulation of p53 Responses: A Comparative Study of Mdm2 and MdmX RING Domains in U2OS Cells.International journal of molecular sciences · 2020Article
- Frequent amplifications of ESR1, ERBB2 and MDM4 in primary invasive lobular breast carcinoma.Cancer letters · 2019Article
- Synergistic repression of thyroid hyperplasia by cyclin C and Pten.Journal of cell science · 2019Article
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- The p53 inhibitor Mdm4 cooperates with multiple genetic lesions in tumourigenesis.The Journal of pathology · 2017Article
- The role of MDM2 and MDM4 in breast cancer development and prevention.Journal of molecular cell biology · 2017Review
- Targeting the NFAT1-MDM2-MDMX Network Inhibits the Proliferation and Invasion of Prostate Cancer Cells, Independent of p53 and Androgen.Frontiers in pharmacology · 2017Article
- Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation.eLife · 2016Article
- TFIIS.h, a new target of p53, regulates transcription efficiency of pro-apoptotic bax gene.Scientific reports · 2016Article
- Targeting RING domains of Mdm2-MdmX E3 complex activates apoptotic arm of the p53 pathway in leukemia/lymphoma cells.Cell death & disease · 2015Article
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 5 institutions in 2 countries.
Funding
Abstract
We have shown previously that MDM2 promotes the degradation of the cyclin-dependent kinase inhibitor p21 through a ubiquitin-independent proteolytic pathway. Here we report that the MDM2 analog, MDMX, also displays a similar activity. MDMX directly bound to p21 and mediated its proteasomal degradation. Although the MDMX effect was independent of MDM2, they synergistically promoted p21 degradation when coexpressed in cells. This degradation appears to be mediated by the 26S proteasome, as MDMX and p21 bound to S2, one of the subunits of the 19S component of the 26S proteasome, in vivo. Conversely, knockdown of MDMX induced the level of endogenous p21 proteins that no longer cofractionated with 26S proteasome, resulting in G(1) arrest. The level of p21 was low at early S phase but markedly induced by knocking down either MDMX or MDM2 in human cells. Ablation of p21 rescued the G(1) arrest caused by double depletion of MDM2 and MDMX in p53-null cells. These results demonstrate that MDMX and MDM2 independently and cooperatively regulate the proteasome-mediated degradation of p21 at the G(1) and early S phases.
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What OpenQuestion holds
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.