ArticleThe EMBO journal1998
Nucleo-cytoplasmic shuttling of the hdm2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein.
Article in The EMBO journal, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 245 papers.
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Who cites it
245 citing papers in PubMed, 608 citations in OpenAlex.
- Review
- Proteasomal proteolysis in p62 condensates directs tumor suppression or growth depending on their subcellular localization.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Black Hole of Immune Checkpoint Blocking Therapy for Gastric Cancer: Hyperprogressive Disease.Cancer science · 2025Review
- LINE1 insertion into the NACC2 locus disrupts the HDM2 axis and activates lung oncogenic signaling.NPJ precision oncology · 2025Article
- The Ubiquitination of Arrestin3 within the Nucleus Triggers the Nuclear Export of Mdm2, Which, in Turn, Mediates the Ubiquitination of GRK2 in the Cytosol.International journal of molecular sciences · 2024Article
- Angiotensin-Converting Enzyme 2 Posttranslational Modifications and Implications for Hypertension and SARS-CoV-2: 2023 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Gene alterations in the nuclear transport receptor superfamily: A study of head and neck cancer.PloS one · 2024Article
- Review
- MDM2 amplification is rare in gastric cancer.Virchows Archiv : an international journal of pathology · 2023Article
- The SWIB/MDM2 motif of UBE4B activates the p53 pathway.Molecular therapy. Nucleic acids · 2023Article
- Exportin Crm1 is important for Swi6 nuclear shuttling and MBF transcription activation in Saccharomyces cerevisiae.BMC molecular and cell biology · 2022Article
- MDM2-Driven Ubiquitination Rapidly Removes p53 from Its Cognate Promoters.Biomolecules · 2021Article
- Mechanisms of TP53 Pathway Inactivation in Embryonic and Somatic Cells-Relevance for Understanding (Germ Cell) Tumorigenesis.International journal of molecular sciences · 2021Review
- Functional display of bioactive peptides on the vGFP scaffold.Scientific reports · 2021Article
- Co-Operativity between MYC and BCL-2 Pro-Survival Proteins in Cancer.International journal of molecular sciences · 2021Review
- Molecular Mechanisms of Senescence and Implications for the Treatment of Myeloid Malignancies.Cancers · 2021Review
- Transition and identification of pathological states in p53 dynamics for therapeutic intervention.Scientific reports · 2021Article
- Article
- The RAS-interacting chaperone UNC119 drives the RASSF6-MDM2-p53 axis and antagonizes RAS-mediated malignant transformation.The Journal of biological chemistry · 2020Article
- MDM2's dual mRNA binding domains co-ordinate its oncogenic and tumour suppressor activities.Nucleic acids research · 2020Article
185 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hdm2 gene is overexpressed in a variety of human tumors. Its gene product localizes predominantly to the nucleus, where it acts as an inhibitor of the p53 tumor suppressor gene product. It is shown here that the hdm2 oncoprotein constantly shuttles between the nucleus and the cytoplasm. Shuttling of hdm2 does not depend on its interaction with p53. Nuclear export of hdm2 is mediated by a signal sequence similar to the nuclear export signal of the rev protein from human immunodeficiency virus and other lentiviruses. Mutation of this signal sequence abolishes detectable nucleo-cytoplasmic shuttling. When fused to a carrier protein, the hdm2 signal sequence can mediate nuclear export after intranuclear microinjection into HeLa cells. The export of hdm2 can be blocked by a competitive inhibitor of rev export, arguing that the export pathways for hdm2 and rev are either overlapping or identical. Inhibition of its export modifies the ability of hdm2 to block p53-mediated transcriptional activation, and hdm2's export function is required to accelerate the degradation of p53. Thus the rev nuclear export pathway may be used to regulate an oncogene product's activity and modulate cellular growth.
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