This discussion is becoming interesting.
I don`t say, that we should not support the "healthy" function of tumor supressing proteins, in that way I am speaking of things like enhancing DNA repair in order to prevent deletion of P53 genes or any unwanted epigenetic changes, but not of boosting the level of P53 in cells, where it is functioning normally or is already overexpressed due to aging.
I have read a review in which the paper mentioning the "super 53mice", which develop less tumors and live to a normal age, was quoted. I have also read the paper now.
The authors of the super P53mice study have worked with other methods, not just implementing P53 cDNA or any modified "superversions" of this protein but a whole segment including introns and other regulating genes. It is indeed interesting, but we should not forget studies in which a stronger P53 function lead to fewer cancers and accelerated aging. So it is note worthy to say that P53 binds to MnSOD in mitochondria, disactivating its function and leading to apoptosis and cell damage, an action which could be a sideeffect of a higher P53 exp
ression. (1) On the other side (mitochondria targeted) telomerase is doing something similar and is also enhancing mitochondrial stress.
I have used resveratrol several times as an example for this very strange behaviour.
Resveratrol is not only supressing P16 but also P53 through activation of SIRT-1 and deacetylation of P53. (2)
Inactivation of Sirt1 and 2 leads to activation of P53. (3)
Furthermore it is deacetylating the retinoblastoma (RB) factor and on this way contributing to the inactivation of RB. (4)
What is really irritating me, is that this compound, resveratrol, is lowering the level and effectivity of 3 important tumor supressor proteins (P53, P16, RB)
and is plus activating telomerase
and despite all of this facts it is: cancer protective
I think this whole stuff is not so easy as it seems, and I would also need time to read more about it, right now I am learning for exams and have a lack of time but I will try to read more after that.
Zhao Y, Chaiswing L, Velez JM, Batinic-Haberle I, Colburn NH, Oberley TD, St Clair DK.
p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase.
Cancer Res. 2005 May 1;65(9):3745-50.
Cao C, Lu S, Kivlin R, Wallin B, Card E, Bagdasarian A, Tamakloe T, Wang WJ, Song X, Chu WM, Kouttab N, Xu A, Wan Y.
SIRT1 confers protection against UVB- and H(2)O(2)-induced cell death via modulation of p53 and JNK in cultured skin keratinocytes.
J Cell Mol Med. 2008 Aug 4. [Epub ahead of print]
Brooks CL, Gu W.
p53 Activation: a case against Sir.
Cancer Cell. 2008 May;13(5):377-8.
Wong S, Weber JD.
Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1.
Biochem J. 2007 Nov 1;407(3):451-60.
Edited by aidanpryde, 30 September 2008 - 04:04 PM.