ArticleProceedings of the National Academy of Sciences of the United States of America2007
PACT is a negative regulator of p53 and essential for cell growth and embryonic development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 114 citations in OpenAlex.
- PACT Inhibits Malignant Biological Behavior of Ovarian Cancer Cells by Regulating TERT Expression.Molecular carcinogenesis · 2026Article
- RBBP6 and cancer: from molecular mechanisms to clinical implications.Frontiers in oncology · 2026Review
- Yellow Fever Virus Interactomes Reveal Common and Divergent Strategies of Replication and Evolution for Mosquito-borne Flaviviruses.bioRxiv : the preprint server for biology · 2025Article
- EIF3D safeguards the homeostasis of key signaling pathways in human primed pluripotency.Science advances · 2025Article
- Rbbp6-Mediated Bmal1 Ubiquitination Inhibits YAP1 Signaling Pathway to Promote Ferroptosis in Diabetes-Induced Testicular Damage.Diabetes & metabolism journal · 2025Article
- Ezetimibe Anticancer Activity via the p53/Mdm2 Pathway.Biomedicines · 2025Article
- Mbnl1-mediated alternative splicing of circMlxipl regulates Rbbp6-involved ChREBP turnover to inhibit lipotoxicity-induced β-cell damage.Molecular medicine (Cambridge, Mass.) · 2024Article
- The role of lipoprotein‑associated phospholipase A2 in inflammatory response and macrophage infiltration in sepsis and the regulatory mechanisms.Functional & integrative genomics · 2024Article
- Article
- Unveiling dysregulated lncRNAs and networks in non-syndromic cleft lip with or without cleft palate pathogenesis.Scientific reports · 2024Article
- LIM domain-containing protein Ajuba inhibits chemotherapy-induced apoptosis by negatively regulating p53 stability in colorectal cancer cells.Molecular oncology · 2023Article
- Expression, purification, and characterisation of the p53 binding domain of Retinoblastoma binding protein 6 (RBBP6).PloS one · 2023Article
- Review
- Cell Death and the p53 Enigma During Mammalian Embryonic Development.Stem cells (Dayton, Ohio) · 2022Review
- RBBP6 activates the pre-mRNA 3' end processing machinery in humans.Genes & development · 2022Article
- Molecular Mechanisms of HIV Protease Inhibitors Against HPV-Associated Cervical Cancer: Restoration ofFrontiers in molecular biosciences · 2022Review
- Developmental Acquisition ofGenes · 2021Review
- N6-methyladenosine (m6A) RNA methylation regulator SNRPC is a prognostic biomarker and is correlated with immunotherapy in hepatocellular carcinoma.World journal of surgical oncology · 2021Article
- Microscale thermophoresis analysis of the molecular interaction between small nuclear ribonucleoprotein polypeptide G and the RING finger domain of RBBP6 towards anti-cancer drug discovery.American journal of translational research · 2021Article
- Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor suppressor p53 regulates cell cycle progression and apoptosis in response to various types of stress, whereas excess p53 activity creates unwanted effects. Tight regulation of p53 is essential for maintaining normal cell growth. p53-associated cellular protein-testes derived (PACT, also known as P2P-R, RBBP6) is a 250-kDa Ring finger-containing protein that can directly bind to p53. PACT is highly up-regulated in esophageal cancer and may be a promising target for immunotherapy. However, the physiological role of the PACT-p53 interaction remains largely unclear. Here, we demonstrate that the disruption of PACT in mice leads to early embryonic lethality before embryonic day 7.5 (E7.5), accompanied by an accumulation of p53 and widespread apoptosis. p53-null mutation partially rescues the lethality phenotype and prolonged survival to E11.5. Endogenous PACT can interact with Hdm2 and enhance Hdm2-mediated ubiquitination and degradation of p53 as a result of the increase of the p53-Hdm2 affinity. Consequently, PACT represses p53-dependent gene transcription. Knockdown of PACT significantly attenuates the p53-Hdm2 interaction, reduces p53 polyubiquitination, and enhances p53 accumulation, leading to both apoptosis and cell growth retardation. Taken together, our data demonstrate that the PACT-p53 interaction plays a critical role in embryonic development and tumorigenesis and identify PACT as a member of negative regulators of p53.
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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.