This is a preprint paper.
"Abstract
... We examined the interaction between SARSCoV-2 spike, p53 and MDM2 (E3 ligase, which mediates p53 degradation) in cancer cells using an immunoprecipitation assay. We observed that SARS-CoV-2 spike protein interrupts p53-MDM2 protein interaction... We further observed that SARS-CoV-2 spike suppresses p53 transcriptional activity in cancer cells... The suppressive effect of SARS-CoV-2 spike on p53-dependent gene activation provides a potential molecular mechanism by which SARS-CoV-2 infection may impact tumorigenesis, tumor progression and chemotherapy sensitivity...
Introduction
... DNA damage or therapy-induced tumor suppressor p53 protein transcriptionally activates genes leading to multiple effects preserving genome integrity, altering metabolism, immune response, cell cycle, DNA repair, cell growth and cell apoptosis to prevent or eliminate transformed cells. Loss of p53 function increases the incidence of carcinogen-induced tumorigenesis and drives chemo-resistance. SARS-CoV-2 infection has been found to alter p53 stabilization...
In this study, we performed cell-based assays to examine the effect of SARS-CoV-2 on p53 activation in cancer cells and demonstrate that SARS-CoV-2 spike interrupts the MDM2-p53 interaction in cancer cells and alters p53 signaling in cancer cells upon chemotherapy included blunted activation of p53 targets involved in growth arrest and apoptosis...
Discussion
... The SARS-CoV-2 spike S2 protein subunit plays a key role in SARS-CoV-2 invasion of human cells through spike S2 binding to receptor angiotensin-converting enzyme 2 (ACE2) on the human host cell surface. We show here that spike S2 can alter p53 transcriptional activity in wild-type p53-expressing cancer cells based on reduction of the p53-responsive reporter activity and a decrease in selected p53 targets such as p21(WAF1) or TRAIL Death Receptor DR5 at the protein level...
The p53 protein is considered as a 'genome guardian' by arresting the cell cycle to repair DNA damage or causing cell death in the presence of unrepaired persistent damage and stress. In our preliminary experiments reported here, the SARS-CoV-2 spike-induced inactivation of p53 was correlated to an apparent reduction of expression of DNA damage response protein g-H2AX after cisplatin exposure and a reduced cell cycle checkpoint response in the cancer cells the SARS-CoV-2 spike causes an altered DNA damage sensing and repair response in cancer cells...
We found that SARS-CoV-2 spike S2 interrupts p53-MDM2 interaction in cancer cells in the absence of exposure to DNA damaging agents...
Our results have implications for the biological effects of spike S2 subunit in human cells whether spike is present due to primary COVID-19 infection or due to mRNA vaccines where its expression is used to promote anti-viral immunity."
This version posted April 15, 2024. It is made available under a CC-BY-NC-ND 4.0 International license.