Are there any conditions where high p21 (cell cycle inhibitor) levels would allow cell proliferation? Not just one duplication, long term culture proliferation.
Could anyone suggest papers?
Thanks!
At a single cell level one could think about a loss-of-function mutation, where p21 would not be able to orchestrate the G1 to S-phase progression.
If you are referring to long-term culture, you have to consider that some cells will enter senescence (mediated by p21) and more and more over time might undergo the same pathway. If the remaining cells are actively proliferating, you might still see an increase in p21 coming from the senescent cells and cell proliferation from the cycling cells. The secretome associated to senescence will also influence the long term of your culture.
Thanks Matteo.
I see your point, but it still seems to me difficult to have a culture growing faster than another and the first expressing more p21: same cell line, different expression construct transduced, indirectly upregulating p21 and growing faster.
I was referring to cells within the same culture (meaning that some cells with a senescent phenotype display high p21 levels comparing to those actively cycling) but of course every experiment has its own variables. What were the cells transduced with?
Could it be that there is just an accumulation of inactive p21? Or that is sequestered and unable to exert its primary function?
There are anyway evidences in the literature of some canine tumors displaying high levels of p21 and increased proflierative capacity of the cells, this might be useful to you. I ti is also known that in normal conditions, p21 is expressed at high levels in tissue with rapid and high tyrnover, like the GI tracts.
Our data show that deficiency in p21 increases clonogenic radiosensitivity in vitro in cells with specific genotypes. With Vogelstein we have shown cells with abrogated p21 are substantially similar to tis parent line in vitro but greatly deficient to radiotherapy as a xenograft tumor. We find, in general, in multiple cells with reduced p21 expression, increased radiosensitivity in vitro and increased radiosensitivity of their xenograft tumors when treated as a xenograft there is increased radiosensitivity distinct from their in vitro radiosensitivity.
You may check p16 and Rb anti-proliferation pathway. Many cell lines in the laboratory loss one of these inhibitors or have mutated copies and become immortalized even they have wild type p21 or p53 expression. You can also check this paper.
Article Novel frameshift mutation in the p16/INK4A tumor suppressor ...
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