The p53-p21-Cyclin D2 regulatory axis drives metabolic reprogramming and a distinct senescent macrophage senotype during aging and MASLD
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
The p53-p21-Cyclin D2 regulatory axis drives metabolic reprogramming and a distinct senescent macrophage senotype during aging and MASLD.
Aging drives chronic disease in part through senescent cells, including macrophages, which fuel inflammation. Senescent macrophages are functionally heterogeneous: canonical p16-high macrophages promo...
www.biorxiv.org
September 29, 2026 at 5:16 PM
The p53-p21-Cyclin D2 regulatory axis drives metabolic reprogramming and a distinct senescent macrophage senotype during aging and MASLD
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
The p53-p21-Cyclin D2 regulatory axis drives metabolic reprogramming and a distinct senescent macrophage senotype during aging and MASLD. https://www.biorxiv.org/content/10.64898/2026.09.22.753597v1
September 28, 2026 at 4:16 PM
The p53-p21-Cyclin D2 regulatory axis drives metabolic reprogramming and a distinct senescent macrophage senotype during aging and MASLD. https://www.biorxiv.org/content/10.64898/2026.09.22.753597v1
Tissues from severe autopsied Covid cases showed reduced p53 expression and increased MDM2 or p21 dysregulation in lung and vascular endothelium. In ACE2-humanized mice and hamsters, infection reduced p53-responsive gene expression (e.g., CDKN1A, GADD45A) in lung tissue during peak viral replication
October 27, 2025 at 12:50 AM
Tissues from severe autopsied Covid cases showed reduced p53 expression and increased MDM2 or p21 dysregulation in lung and vascular endothelium. In ACE2-humanized mice and hamsters, infection reduced p53-responsive gene expression (e.g., CDKN1A, GADD45A) in lung tissue during peak viral replication
Of course, given that we know SARS-CoV-2 inhibits the tumour suppressor effects of p53, COVID is a putative cancer risk factor in its own right. www.oncotarget.com/article/2858...
Transfected SARS-CoV-2 spike DNA for mammalian cell expression inhibits p53 activation of p21(WAF1), TRAIL Death Receptor DR5 and MDM2 proteins in cancer... | Oncotarget
https://doi.org/10.18632/oncotarget.28582 Shengliang Zhang, Wafik S. El-Deiry
www.oncotarget.com
June 28, 2025 at 11:42 AM
Of course, given that we know SARS-CoV-2 inhibits the tumour suppressor effects of p53, COVID is a putative cancer risk factor in its own right. www.oncotarget.com/article/2858...
“Znhit3 regulates p53/p21 signaling and governs cerebellar granule cell development”
Online in CDD: www.nature.com/articles/s41...
Online in CDD: www.nature.com/articles/s41...
Znhit3 regulates p53/p21 signaling and governs cerebellar granule cell development - Cell Death & Differentiation
Cell Death & Differentiation - Znhit3 regulates p53/p21 signaling and governs cerebellar granule cell development
www.nature.com
March 24, 2026 at 12:04 PM
“Znhit3 regulates p53/p21 signaling and governs cerebellar granule cell development”
Online in CDD: www.nature.com/articles/s41...
Online in CDD: www.nature.com/articles/s41...
Much being made of this paper by antivax eejits.
Without going through the data, which I have, folks seem to miss one pretty fundamental point...
How, exactly, does a membrane protein (SARS2 spike) interrupt p53 interactions occurring in the nucleus? 🤔
pubmed.ncbi.nlm.nih.gov/38709242/?s=09
Without going through the data, which I have, folks seem to miss one pretty fundamental point...
How, exactly, does a membrane protein (SARS2 spike) interrupt p53 interactions occurring in the nucleus? 🤔
pubmed.ncbi.nlm.nih.gov/38709242/?s=09
Transfected SARS-CoV-2 spike DNA for mammalian cell expression inhibits p53 activation of p21(WAF1), TRAIL Death Receptor DR5 and MDM2 proteins in cancer cells and increases cancer cell viability afte...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 infection has led to worsened outcomes for patients with cancer. SARS-CoV-2 spike protein mediates host cell infection and cel...
pubmed.ncbi.nlm.nih.gov
May 27, 2025 at 7:31 PM
Much being made of this paper by antivax eejits.
Without going through the data, which I have, folks seem to miss one pretty fundamental point...
How, exactly, does a membrane protein (SARS2 spike) interrupt p53 interactions occurring in the nucleus? 🤔
pubmed.ncbi.nlm.nih.gov/38709242/?s=09
Without going through the data, which I have, folks seem to miss one pretty fundamental point...
How, exactly, does a membrane protein (SARS2 spike) interrupt p53 interactions occurring in the nucleus? 🤔
pubmed.ncbi.nlm.nih.gov/38709242/?s=09
Senescence can be p53/p21- AND p16-independent😮(Though they are induced as bystander markers)
p300 HAT inhibition in fibroblasts
❎DDR
✅G2/M arrest
✅SAHF
#NatureComms 2011
www.nature.com/articles/nco...
p300 HAT inhibition in fibroblasts
❎DDR
✅G2/M arrest
✅SAHF
#NatureComms 2011
www.nature.com/articles/nco...
February 20, 2026 at 12:39 PM
Senescence can be p53/p21- AND p16-independent😮(Though they are induced as bystander markers)
p300 HAT inhibition in fibroblasts
❎DDR
✅G2/M arrest
✅SAHF
#NatureComms 2011
www.nature.com/articles/nco...
p300 HAT inhibition in fibroblasts
❎DDR
✅G2/M arrest
✅SAHF
#NatureComms 2011
www.nature.com/articles/nco...
The p53-p21-Cyclin D2 regulatory axis drives metabolic reprogramming and a distinct senescent macrophage senotype during aging and MASLD. https://www.biorxiv.org/content/10.64898/2026.09.22.753597v1
September 28, 2026 at 4:16 PM
The p53-p21-Cyclin D2 regulatory axis drives metabolic reprogramming and a distinct senescent macrophage senotype during aging and MASLD. https://www.biorxiv.org/content/10.64898/2026.09.22.753597v1
#Replication stress-associated p21 expression marks proliferating juvenile #osteoblasts within a Hedgehog-dependent niche, while c-Myc activation and p53 loss cooperate to drive Hedgehog-independent #osteosarcoma formation doi.org/10.1038/s414...
June 29, 2026 at 11:27 AM
#Replication stress-associated p21 expression marks proliferating juvenile #osteoblasts within a Hedgehog-dependent niche, while c-Myc activation and p53 loss cooperate to drive Hedgehog-independent #osteosarcoma formation doi.org/10.1038/s414...
FYI: p53 and p21 do WAY MORE than just senescence and death.
Then don't say you weren't warned.
Then don't say you weren't warned.
November 23, 2024 at 9:06 PM
FYI: p53 and p21 do WAY MORE than just senescence and death.
Then don't say you weren't warned.
Then don't say you weren't warned.
It'd also be a good time for them to learn about things like p53-p21 signalling, how SARS-COV-2 interacts with it, and how that relates to Li-Fraumeni Syndrome in the context of repeated, persistent infection.
Among a much longer list (random recent review):
link.springer.com/article/10.1...
Among a much longer list (random recent review):
link.springer.com/article/10.1...
Oncogenic potential of SARS-CoV-2—targeting hallmarks of cancer pathways - Cell Communication and Signaling
The 2019 outbreak of SARS-CoV-2 has caused a major worldwide health crisis with high rates of morbidity and death. Interestingly, it has also been linked to cancer, which begs the issue of whether it ...
link.springer.com
March 24, 2025 at 5:34 AM
It'd also be a good time for them to learn about things like p53-p21 signalling, how SARS-COV-2 interacts with it, and how that relates to Li-Fraumeni Syndrome in the context of repeated, persistent infection.
Among a much longer list (random recent review):
link.springer.com/article/10.1...
Among a much longer list (random recent review):
link.springer.com/article/10.1...
New work from the lab: Identification of CNOT1-CCR4-NOT as a suppressor of 53BP1-p53-p21 signaling @cp-cellreports.bsky.social. Congratulations to first author Antonio Galarreta and to all co-authors. www.cell.com/cell-reports.... #Microscopy #RNAiScreen #Condensates
July 31, 2025 at 2:09 PM
New work from the lab: Identification of CNOT1-CCR4-NOT as a suppressor of 53BP1-p53-p21 signaling @cp-cellreports.bsky.social. Congratulations to first author Antonio Galarreta and to all co-authors. www.cell.com/cell-reports.... #Microscopy #RNAiScreen #Condensates
Another exciting research article from a member of the #RepliFate network!
The Altmeyer lab identified the CNOT1-CCR4-NOT complex as a multi-level suppressor of the 53BP1-p53-p21 signaling axis.
Check out their findings here: doi.org/10.1016/j.ce...
The Altmeyer lab identified the CNOT1-CCR4-NOT complex as a multi-level suppressor of the 53BP1-p53-p21 signaling axis.
Check out their findings here: doi.org/10.1016/j.ce...
August 11, 2025 at 9:26 AM
Another exciting research article from a member of the #RepliFate network!
The Altmeyer lab identified the CNOT1-CCR4-NOT complex as a multi-level suppressor of the 53BP1-p53-p21 signaling axis.
Check out their findings here: doi.org/10.1016/j.ce...
The Altmeyer lab identified the CNOT1-CCR4-NOT complex as a multi-level suppressor of the 53BP1-p53-p21 signaling axis.
Check out their findings here: doi.org/10.1016/j.ce...
Exploring unsettled biomolecular interactions with an NMR twist. A joint effort with the Obsil lab. www.nature.com/articles/s41...
Structural plasticity of the FOXO-DBD:p53-TAD interaction - Nature Communications
Interactions between human transcription factors Forkhead box O4 (FOXO4) and p53 promote cellular senescence and activate p21 transcription. Here, the AUs use NMR to characterise the transient nature ...
www.nature.com
May 28, 2025 at 5:55 AM
Exploring unsettled biomolecular interactions with an NMR twist. A joint effort with the Obsil lab. www.nature.com/articles/s41...
P53 activation is a hallmark of genome instability, but what triggers it is unclear. Using a rapid degron-based system of chromosome mis-segregation we observe emergence of abnormal nuclear shape and mechanics, p53/p21 activation, and cell cycle arrest. Are these two processes are related and how?
January 8, 2025 at 12:14 PM
P53 activation is a hallmark of genome instability, but what triggers it is unclear. Using a rapid degron-based system of chromosome mis-segregation we observe emergence of abnormal nuclear shape and mechanics, p53/p21 activation, and cell cycle arrest. Are these two processes are related and how?
Are you aware of any serious examination of the impacts of inhibition of p53-p21 signalling by SARS-CoV-2?
Mechanistically, increased cancer is 👉the expected outcome👈 of repeated, persistent exposures to the virus (see e.g. Li-Fraumeni Syndrome).
scholar.google.com/scholar?q=SA...
Mechanistically, increased cancer is 👉the expected outcome👈 of repeated, persistent exposures to the virus (see e.g. Li-Fraumeni Syndrome).
scholar.google.com/scholar?q=SA...
Google Scholar
scholar.google.com
November 18, 2024 at 1:02 AM
Are you aware of any serious examination of the impacts of inhibition of p53-p21 signalling by SARS-CoV-2?
Mechanistically, increased cancer is 👉the expected outcome👈 of repeated, persistent exposures to the virus (see e.g. Li-Fraumeni Syndrome).
scholar.google.com/scholar?q=SA...
Mechanistically, increased cancer is 👉the expected outcome👈 of repeated, persistent exposures to the virus (see e.g. Li-Fraumeni Syndrome).
scholar.google.com/scholar?q=SA...
XPO1 Inhibition by Selinexor Induces Nuclear p53 and p21 Accumulation, Cell-Cycle Arrest and Apoptosis in Testicular Germ Cell Tumors https://www.biorxiv.org/content/10.64898/2026.09.14.750914v1
September 21, 2026 at 3:49 AM
XPO1 Inhibition by Selinexor Induces Nuclear p53 and p21 Accumulation, Cell-Cycle Arrest and Apoptosis in Testicular Germ Cell Tumors https://www.biorxiv.org/content/10.64898/2026.09.14.750914v1
Restoration of nuclear mechanophenotype indeed prevents p53/p21 activation and cell cycle arrest. Conversely, experimentally elevating nuclear envelope tension with mechano-osmotic forces is sufficient to trigger the pathway, directly linking nuclear envelope mechanics to p53 checkpoint.
January 8, 2025 at 12:14 PM
Restoration of nuclear mechanophenotype indeed prevents p53/p21 activation and cell cycle arrest. Conversely, experimentally elevating nuclear envelope tension with mechano-osmotic forces is sufficient to trigger the pathway, directly linking nuclear envelope mechanics to p53 checkpoint.
Ritu Agrawal and Sagar Sengupta show that p53 can directly regulate gene repression via the DREAM complex independently of p21 in asynchronously growing cells
www.embopress.org/doi/full/10....
www.embopress.org/doi/full/10....
March 5, 2025 at 7:35 PM
Ritu Agrawal and Sagar Sengupta show that p53 can directly regulate gene repression via the DREAM complex independently of p21 in asynchronously growing cells
www.embopress.org/doi/full/10....
www.embopress.org/doi/full/10....
Hello 7 followers! Ever wonder why cells of the same type tend to have a pretty uniform size? Check out our new paper out in @MolecularCell today to find out why too big can be a bad thing in terms of genome homeostasis and proliferative potential.
www.cell.com/molecular-ce...
www.cell.com/molecular-ce...
Genome homeostasis defects drive enlarged cells into senescence
Manohar et al. studied how increased cell size—a hallmark of senescence—impairs long-term
proliferation. Excess cell size activates p53-p21 signaling and impairs 53BP1 recruitment
to DNA double-s...
www.cell.com
November 16, 2023 at 5:17 PM
Hello 7 followers! Ever wonder why cells of the same type tend to have a pretty uniform size? Check out our new paper out in @MolecularCell today to find out why too big can be a bad thing in terms of genome homeostasis and proliferative potential.
www.cell.com/molecular-ce...
www.cell.com/molecular-ce...
An intriguing paper linking Senescence with tumor Cell cycle re-entry & Recurrence👇
Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing
Jiri Bartek & Vassilis Gorgoulis labs @naturecellbiology.bsky.social 2016
www.nature.com/articles/ncb...
Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing
Jiri Bartek & Vassilis Gorgoulis labs @naturecellbiology.bsky.social 2016
www.nature.com/articles/ncb...
December 6, 2024 at 12:46 PM
An intriguing paper linking Senescence with tumor Cell cycle re-entry & Recurrence👇
Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing
Jiri Bartek & Vassilis Gorgoulis labs @naturecellbiology.bsky.social 2016
www.nature.com/articles/ncb...
Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing
Jiri Bartek & Vassilis Gorgoulis labs @naturecellbiology.bsky.social 2016
www.nature.com/articles/ncb...
Finally, we addressed how nuclear envelope stress is sensed. Inhibitor screen revealed that AKT and ATR were required for p53/p21 activation. Importantly, this mechanosensitive #checkpoint is relevant in diseases associated with #genome instability and perturbed nuclear shape, such as #progeria.
January 8, 2025 at 12:14 PM
Finally, we addressed how nuclear envelope stress is sensed. Inhibitor screen revealed that AKT and ATR were required for p53/p21 activation. Importantly, this mechanosensitive #checkpoint is relevant in diseases associated with #genome instability and perturbed nuclear shape, such as #progeria.
It's concerning that COVID interferes with p53-p21 signalling, and the Dunning-Kruger medical admin types running public health and IPC didn't even bother to understand what that means before deciding to let COVID rip.
What's repeated, persistent infection with that doing to a generation of kids?
What's repeated, persistent infection with that doing to a generation of kids?
The worst part of the potential for COVID to cause cancer is that it's entirely predictable, but the medical policy types have to control everything, so they locked science out of the room and tried to wing it.
Dunning-Kruger pandemic.
Dunning-Kruger pandemic.
June 23, 2025 at 4:35 AM
It's concerning that COVID interferes with p53-p21 signalling, and the Dunning-Kruger medical admin types running public health and IPC didn't even bother to understand what that means before deciding to let COVID rip.
What's repeated, persistent infection with that doing to a generation of kids?
What's repeated, persistent infection with that doing to a generation of kids?
RRIDs were included in this in Molecular Oncology paper. RRIDs improve reproducibility in scientific research. #BetterScience #RRID #STMpublishing
CDK11 inhibition induces cytoplasmic p21 WAF1 splice variant by p53 stabilisation and SF3B1 inactivation
Read the full paper: CDK11 inhibition induces cytoplasmic p21 WAF1 splice variant by p53 stabilisation and SF3B1 inactivation
doi.org
April 5, 2026 at 7:00 AM
RRIDs were included in this in Molecular Oncology paper. RRIDs improve reproducibility in scientific research. #BetterScience #RRID #STMpublishing
I have to say I am not looking forward to learning what repeated, persistent infection with a virus (SARS-CoV-2) that appears to interfere with p53-p21 signalling does to everyone.
If I put that question on an oncology exam, there'd be an obvious answer.
scholar.google.com/scholar?hl=e...
If I put that question on an oncology exam, there'd be an obvious answer.
scholar.google.com/scholar?hl=e...
Google Scholar
scholar.google.com
February 5, 2025 at 9:11 AM
I have to say I am not looking forward to learning what repeated, persistent infection with a virus (SARS-CoV-2) that appears to interfere with p53-p21 signalling does to everyone.
If I put that question on an oncology exam, there'd be an obvious answer.
scholar.google.com/scholar?hl=e...
If I put that question on an oncology exam, there'd be an obvious answer.
scholar.google.com/scholar?hl=e...