The p53 tumour suppressor is activated by numerous stressors to induce apoptosis, cell cycle arrest, or senescence. To study the biological effects of altered p53 function, we generated mice with a deletion mutation in the first six exons of the p53 gene that express a truncated RNA capable of encoding a carboxy-terminal p53 fragment. This mutation confers phenotypes consistent with activated p53 rather than inactivated p53. Mutant (p53+/m) mice exhibit enhanced resistance to spontaneous tumours compared with wild-type (p53+/+) littermates. As p53+/m mice age, they display an early onset of phenotypes associated with ageing. These include reduced longevity, osteoporosis, generalized organ atrophy and a diminished stress tolerance. A second line of transgenic mice containing a temperature-sensitive mutant allele of p53 also exhibits early ageing phenotypes. These data suggest that p53 has a role in regulating organismal ageing.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. Methods: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. Results: The median age was 40 years (range, 20-73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required J Korean Med Sci. 2020 Apr 6;35(13):e142 https://doi.

The Wip1 gene is a serine/threonine phosphatase that is induced in a p53-dependent manner by DNAdamaging agents. We show here that Wip1 message is expressed in moderate levels in all organs, but is present at very high levels in the testes, particularly in the postmeiotic round spermatid compartment of the seminiferous tubules. We have confirmed that Wip1 mRNA is induced by ionizing radiation in mouse tissues in a p53-dependent manner. To further determine the normal biological function of Wip1 in mammalian organisms, we have generated Wip1-deficient mice. Wip1 null mice are viable but show a variety of postnatal abnormalities, including variable male runting, male reproductive organ atrophy, reduced male fertility, and reduced male longevity. Mice lacking Wip1 show increased susceptibility to pathogens and diminished T-and B-cell function. Fibroblasts derived from Wip1 null embryos have decreased proliferation rates and appear to be compromised in entering mitosis. The data are consistent with an important role for Wip1 in spermatogenesis, lymphoid cell function, and cell cycle regulation.The p53 tumor suppressor protein plays a critical role in integration of signals that regulate cell growth and death in response to a variety of stressors (11,12,26). Loss or mutation of the gene encoding the p53 protein predisposes a cell to neoplastic transformation (8,21,23). Mutation of the p53 gene has been observed in half of all human cancers, and loss of p53 signaling may play a role in over 80% of all tumors (8,12,13).In response to a variety of cell stresses, including DNA damage, aberrantly activated oncogenes, and hypoxia, p53 is phosphorylated on multiple serine and threonine residues, becomes stabilized, and accumulates in the nucleus (11,12,26). The activated p53 protein is a transcription factor that can upregulate as well as downregulate a battery of genes which participate in the biological response to the cell stress. This response can be in the form of cell cycle arrest, apoptosis, differentiation, or senescence. Any of these responses are likely to prevent the outgrowth of a nascent cancer cell.Among the many p53 transcriptional targets that have recently been identified is the wild-type p53-induced phosphatase (Wip1) (5). The Wip1 gene exhibits a close similarity to type 2C phosphatases (2, 5). The type 2C phosphatases are distinguished from the PP1, PP2A, and PP2B phosphatases by their insensitivity to phosphatase inhibitors such as okadaic acid and requirement for divalent cations (Mg 2ϩ or Mn 2ϩ ) (3, 15). The type 2C phosphatases have been identified in a wide range of organisms and have often been associated with stress response, sexual differentiation, and cell cycle control (3, 15).The Wip1 gene was originally identified in a screen for p53 target genes (5). Wip1 was shown to be upregulated in a p53-dependent manner by ionizing radiation (IR) and by UV radiation (UV) (5, 25). Following IR, Wip1 mRNA was rapidly induced and the protein was localized to the nucleus. The first specific target of the W...