The transcription factor E2F links the RB pathway to the p53 pathway upon loss of function of pRB, thereby playing a pivotal role in the suppression of tumorigenesis. E2F fulfills a major role in cell proliferation by controlling a variety of growth-associated genes. The activity of E2F is controlled by the tumor suppressor pRB, which binds to E2F and actively suppresses target gene expression, thereby restraining cell proliferation. Signaling pathways originating from growth stimulative and growth suppressive signals converge on pRB (the RB pathway) to regulate E2F activity. In most cancers, the function of pRB is compromised by oncogenic mutations, and E2F activity is enhanced, thereby facilitating cell proliferation to promote tumorigenesis. Upon such events, E2F activates the tumor suppressor gene, leading to activation of the tumor suppressor p53 to protect cells from tumorigenesis. ARF inactivates MDM2, which facilitates degradation of p53 through proteasome by ubiquitination (the p53 pathway). P53 suppresses tumorigenesis by inducing cellular senescence or apoptosis. Hence, in almost all cancers, the p53 pathway is also disabled. Here we will introduce the canonical functions of the RB-E2F-p53 pathway first and then the non-classical functions of each component, which may be relevant to cancer biology.
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http://dx.doi.org/10.3390/biology12121511 | DOI Listing |
J Environ Manage
December 2024
Institute of Urology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, China. Electronic address:
Titanium dioxide nanoparticles (TiO NPs) are among the most prevalent nanomaterials utilized in industrial and medical fields. However, their impact on spermatogenesis and male fertility remains insufficiently characterized. This study addresses the reproductive toxicity of TiO NPs and elucidates the underlying molecular mechanisms involved.
View Article and Find Full Text PDFClin Epigenetics
December 2024
Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
Background: Pancreatic adenocarcinoma (PDAC) exhibits a complex microenvironment with diverse cell populations influencing patient prognosis. Single-cell RNA sequencing (scRNA-seq) was used to identify prognosis-related cell types, and DNA methylation (DNAm)-based models were developed to predict outcomes based on their cellular characteristics.
Methods: We integrated scRNA-seq, bulk data, and clinical information to identify key cell populations associated with prognosis.
J Ethnopharmacol
December 2024
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, China. Electronic address:
Steroids
December 2024
Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address:
Toad venom, a family of toxic yet pharmacologically valuable biotoxins, has long been utilized in traditional medicine and holds significant promise in modern drug development. Bufotalin, a prominent bufotoxin, has demonstrated potent cytotoxic properties through mechanisms such as apoptosis induction, cell cycle arrest, endoplasmic reticulum stress activation, and inhibition of metastasis by modulating key pathways including Akt, p53, and STAT3/EMT signaling-these multi-target mechanisms position bufotalin as a promising agent to combat multidrug resistance in cancer therapy. Additionally, advances in bufotalin synthesis, including chemical and biocatalytic methods, have streamlined production, with strategies such as C14-α-hydroxylation and novel coupling techniques enhancing yield and reducing environmental impact.
View Article and Find Full Text PDFSci Total Environ
December 2024
School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China. Electronic address:
Environmental heavy metal contamination, combined with inappropriate use of fungicides, has led to the co-existence of lead (Pb) and iprodione (IPR), presenting signification risks to ecosystems and human health. The toxic effects resulting from concurrent exposure to Pb and IPR, however, remain poorly understood. In the study, we conducted a comprehensive 60-day subchronic study to investigate the toxic effects on the liver and gut in parental male zebrafish through employing multi-omics analyses.
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