P-53 in papers

P53 is kind of a big deal in the literature and it is hard to pick just one paper to look at but here are 3 that focus on P53's function and chemistry



http://www.cbi.pku.edu.cn/chinese/documents/cell/xibaoshengwuxuecankaowenxian/cocb/13/13-3/13(3)-12.pdf

      This review paper focuses mainly on regulation and function of P53. As most people know P53 is the cancer protein, It's main function is to repair damaged cell DNA. It does this by first stoping cell cycle and then either repairing the damaged DNA or causing apoptosis. Once P53 detects DNA damage it acts as a transcription factor activating other proteins. It has a multifaceted response though and the exact mechanism that it uses to trigger apoptosis is not entirely known.

There are numerous regulators of P53 the main enzyme that this paper talks about is MDM2(Mouse double minute 2 homolog). MDM2 both acts as an inhibitor for P53 and a agent for degradation. P53 must be in the nucleus in order to have an effect. MDM2 will ubiqunate both itself and P53 targeting it for nuclear export and degradation. 

http://genesdev.cshlp.org/content/12/18/2831.full.pdf+html

This is a primary research paper that talks about the mechanism for P53 activation.  Cell damage leads to both acetylation and phosphorylation of P53. Two different histone acetyltransferases, theses acetylate lys residues in the carboxyl terminus of P53. This in turn adds to P53's DNA affinity and it's activity as a transcription factor. The paper also mentions the phosphorylation of two serine residues in activating P53.

http://www.nature.com/onc/journal/v24/n17/full/1208615a.html

The last review paper talks about the complexity of P53 and the pathways that it influences. Because cell replication is such a complicated process P53 has to effect many different proteins in order to do it's job. This paper metions over ten feedback loops that P53 is directly involved in. Six of these are directly involved with MDM2, P53s main regulatory protien but there are many more. Some listed are Wnt-beta-catenin, IGF-1-AKT, Rb-E2F, p38 MAP kinase, cyclin-cdk, p14/19 ARF pathways and the cyclin G-PP2A, and p73 gene product. The figure below should give you an idea of just how many different cycles P53 is involved in.

molecule of the month link: http://www.rcsb.org/pdb/101/motm.do?momID=31&evtc=Suggest&evta=Moleculeof%20the%20Month&evtl=TopBar