ArticleThe Journal of biological chemistry2010
HDMX-L is expressed from a functional p53-responsive promoter in the first intron of the HDMX gene and participates in an autoregulatory feedback loop to control p53 activity.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 51 citations in OpenAlex.
- Structure and function of MDM2 and MDM4 in health and disease.The Biochemical journal · 2025Review
- Cellular carcinogenesis in preleukemic conditions:drivers and defenses.Fukushima journal of medical science · 2024Review
- MDMX Regulates Transcriptional Activity of p53 and FOXO Proteins to Stimulate Proliferation of Melanoma Cells.Cancers · 2022Article
- CircSCAP interacts with SF3A3 to inhibit the malignance of non-small cell lung cancer by activating p53 signaling.Journal of experimental & clinical cancer research : CR · 2022Article
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- MDMX inhibits casein kinase 1α activity and stimulates Wnt signaling.The EMBO journal · 2020Article
- Mutant p53 as an Antigen in Cancer Immunotherapy.International journal of molecular sciences · 2020Review
- p53 is regulated by aerobic glycolysis in cancer cells by the CtBP family of NADH-dependent transcriptional regulators.Science signaling · 2020Article
- Targeting MDMX for Cancer Therapy: Rationale, Strategies, and Challenges.Frontiers in oncology · 2020Review
- Specific allelic variants of SNPs in theOncotarget · 2019Article
- The long and the short of it: the MDM4 tail so far.Journal of molecular cell biology · 2019Review
- Targeting apoptosis in acute myeloid leukaemia.British journal of cancer · 2017Review
- Optimal Affinity Enhancement by a Conserved Flexible Linker Controls p53 Mimicry in MdmX.Biophysical journal · 2017Article
- p53 binds the mdmx mRNA and controls its translation.Oncogene · 2017Article
- Negative auto-regulators trap p53 in their web.Journal of molecular cell biology · 2017Review
- The role of MDM2 and MDM4 in breast cancer development and prevention.Journal of molecular cell biology · 2017Review
- Intra molecular interactions in the regulation of p53 pathway.Translational cancer research · 2016Article
- MDM2 oligomers: antagonizers of the guardian of the genome.Oncogene · 2016Review
- Multiplex enhancer-reporter assays uncover unsophisticated TP53 enhancer logic.Genome research · 2016Article
- The Roles of MDM2 and MDMX in Cancer.Annual review of pathology · 2016Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 4 countries.
Funding
Abstract
The p53 regulatory network is critically involved in preventing the initiation of cancer. In unstressed cells, p53 is maintained at low levels and is largely inactive, mainly through the action of its two essential negative regulators, HDM2 and HDMX. p53 abundance and activity are up-regulated in response to various stresses, including DNA damage and oncogene activation. Active p53 initiates transcriptional and transcription-independent programs that result in cell cycle arrest, cellular senescence, or apoptosis. p53 also activates transcription of HDM2, which initially leads to the degradation of HDMX, creating a positive feedback loop to obtain maximal activation of p53. Subsequently, when stress-induced post-translational modifications start to decline, HDM2 becomes effective in targeting p53 for degradation, thus attenuating the p53 response. To date, no clear function for HDMX in this critical attenuation phase has been demonstrated experimentally. Like HDM2, the HDMX gene contains a promoter (P2) in its first intron that is potentially inducible by p53. We show that p53 activation in response to a plethora of p53-activating agents induces the transcription of a novel HDMX mRNA transcript from the HDMX-P2 promoter. This mRNA is more efficiently translated than that expressed from the constitutive HDMX-P1 promoter, and it encodes a long form of HDMX protein, HDMX-L. Importantly, we demonstrate that HDMX-L cooperates with HDM2 to promote the ubiquitination of p53 and that p53-induced HDMX transcription from the P2 promoter can play a key role in the attenuation phase of the p53 response, to effectively diminish p53 abundance as cells recover from stress.
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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.