Damage checkpoint
p53
Also searched as p53.
Vigilant, not trigger-happy: firm tumor-suppression protects you, while over-activation hastens cellular aging.
In depth
The guardian of the genome — it halts damaged cells from dividing and orders the irreparable to stand down.
What drives it
Oxidative stress increases it.
Achanta & Huang 2004, Cancer Res — ROS-generating agents cause oxidative DNA damage that stabilizes and activates p53 (via ATM/ATR-Chk phosphorylation). doi:10.1158/0008-5472.CAN-04-0494. ROS is dose-dependent: physiological ROS signals, excess ROS damages. 'Lower ROS' is therefore not universally desirable. Verified: oxidants activate p53 among the redox-responsive transcription factors; p53 is also subject to Ref-1 redox regulation. doi 10.1158/0008-5472.CAN-04-0494.
DNA integrity increases it.
p53 is normally held at low levels by continuous MDM2-driven degradation; damage is what stabilizes it. On double-strand breaks ATM autophosphorylates and phosphorylates p53 at Ser15, and the ATM/CHK2 and ATR/CHK1 arms converge on p53 as their major downstream effector, producing G1 arrest through p21 (Free Radic Biol Med 2021; Blood 2018;131:488). Shown by blocking both ends: the ATM inhibitor caffeine rescued damage-induced arrest, and silencing p53 with siRNA attenuated it. PMC3660384
Ionizing radiation increases it.
Double-strand breaks activate ATM kinase, which phosphorylates and stabilizes p53. doi 10.1002/hep4.1815
What it drives
It increases Cell turnover.
Nakano & Vousden 2001, Mol Cell 7:683 — p53 induces PUMA (BH3-only), triggering mitochondrial apoptosis. PMID 11463392
It increases Clears worn-out cells.
Role of p53 in Cellular Senescence 2020 — p53 transactivates p21/CDKN1A, enforcing the cell-cycle arrest of senescence. PMID 32182711
It reduces Cell survival.
p53 suppresses transformation by removing the proliferative OR survival capacity of cells carrying DNA damage or driving inappropriate cell-cycle progression — it is the switch that decides a damaged cell should not continue (PMC5287062). Loss or mutation of TP53 inhibits senescence, apoptosis and DNA repair, promoting self-renewal while impairing elimination of damaged cells (PMC7422622). Survival is not always the desirable direction: this pathway is why. PMC5287062
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.