All normal cells express basal low levels of p53 protein and these low levels of the p53, depending upon the approach used to detect it, can be detected. p53 protein levels increase transiently in normal cells upon sensing stress signal and the increase is in part due to stabilization of the protein following its phosphorylation in the N-terminus. However, increased constitutive levels of the p53 protein in cells are tolerated when the protein is functionally inactivated through a number of mechanisms. In light of the above general information, it is conceivable that increased levels of p53 in certain cell types that have lost to regulate cell cycle are associated with cell proliferation. Notably, p53 protein levels increase in quiescent cells upon serum stimulation of cells, which allows cells to enter into cell cycle.

I agree with Prof. Divaker. I want to ask one more thing. Usually when p53 is upregulated in response to stress signal/DNA damage, cells undergo senescence or apoptosis depending on the damaged condition. If its senescence, do the cells become ki-67 negative? Ki-67 negative cells are usually thought as quiescent. Is it possible to correlate p53 upregulation and ki-67 positiveness in quiescent cells when they enter into cycle? In literature, I found ki67 is usually used as a proliferation marker in pathological examination. But I was wondering whether we can use it as an indication of rapidly proliferating cells? Because ki67 is detected in all the phase of cell cycle except Go whereas BrdU/Edu incorporation can shed light onto rapidly dividing cells.

I would like to add a bit of information to what Prof. Divaker neatly explained. Mutant, inactive p53 usually accumulates because of the inability of the cell to get rid of it (e.g., mutations that alter its conformation or lead to misfolding keep it from interacting with MDM2 and thus from being ubiquitinated). A basal level of p53 is necessary for cell cycle progression, but is not coupled to post-translational modifications involved in stress response. Proliferation itself, however, pose treats to the cell, in form of replicative stress (especially true for transformed cells, all of which are to some extent genetically unstable). If the pathways involved in p53 transcriptional regulation upon stress are still working, mutant p53 may still be induced in proliferating cells, but it would not exert its function, being inactive, and would accumulate, being the cell unable to degrade it.

Thanks for the answers. But my question was more in regards to the specific accumulation of mutant p53 in proliferating but not resting, quiescent, G0, differentiated or whatever you want to call it cells. MDM2 might be a lead but I am not sure which cells express MDM2: proliferating or quiescent cells. 

I am not sure about wild type p53 activation and accumulation. I think this should be coinciding with loss of Ki67 expression but that may depend at what phase of the cell cycle this happens. If the cell was in G0/quiescent and the damage occurs, will p53 be activated? I am sure this has been studied for wild type p53. At least in vitro it was shown that wild type p53 can be induced in "normal" cells by DNA damage inducing drugs (DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence.

Leontieva OV1, Blagosklonny MV. Aging (Albany NY). 2010 Dec;2(12):924-35.). What this means for in vivo, I am not sure. What this means for mutant p53, I am not sure either. My observation/impression is that mutant p5 generally does not show up in quiescent or Ki67 positive cells...So how does this work?