Why are tumor suppressor proteins down regulated in cancer cells even they are not mutated.
Can some one explain signaling for this down regulation of tumor suppressor protein with any example or provide literature about this.
The down regulation of TS proteins and genes are crucial for cancer progression. Cancer cells also activate oncogones, which are responsible for sending growth signals, resulting in cell proliferation.
In fact, you don't need a mutation to render the gene inactive. You have several ways to silence a gene without having a mutation.
Now, how this happens is indeed complex.
Basically, you have to think in three ways:
DNA level: Epigenetics - DNA polimerase needs a sequence of DNA to start; however, this sequence can be packed (''hidden''), and thus no transcription happens. You have several enzymes that acytelates histones. In some cases, you over expression of gene that is an inhibitor of your target gene.
RNA level: Degradation of RNA by Rnai; splicing, RNA processing (poli A tail, CAP);
Protein level: Phosphorylation, ubiquitination and post translatational modifications that leads to protein degradation.
This process is way more complex than I said - for that I recommend the following articles:
http://www.ncbi.nlm.nih.gov/pubmed/11932736
http://www.hindawi.com/journals/tswj/2014/896206/
http://www.ncbi.nlm.nih.gov/pubmed/21802130
http://carcin.oxfordjournals.org/content/26/2/487.full.pdf
http://www.scielo.br/pdf/bjmbr/v32n7/3408c.pdf
I hope this articles will provide you the detail of the predicted mechanism of oncogene in regulating tumor suppressor genes. Good luck
It is known that the functional loss of tumor suppressors (TS) provides cancer cells with growth, proliferation, or survival advantage. Further, several mechanisms are known through which TS are functionally inactivated in cancer cells. One of the mechanisms, which is common for a number of TS is decreases in protein levels. Interestingly, more than one mechanism can contribute to functional inactivation of tumor suppressors in cancer cells.
The down regulation of TS proteins and genes are crucial for cancer progression. Cancer cells also activate oncogones, which are responsible for sending growth signals, resulting in cell proliferation.
In fact, you don't need a mutation to render the gene inactive. You have several ways to silence a gene without having a mutation.
Now, how this happens is indeed complex.
Basically, you have to think in three ways:
DNA level: Epigenetics - DNA polimerase needs a sequence of DNA to start; however, this sequence can be packed (''hidden''), and thus no transcription happens. You have several enzymes that acytelates histones. In some cases, you over expression of gene that is an inhibitor of your target gene.
RNA level: Degradation of RNA by Rnai; splicing, RNA processing (poli A tail, CAP);
Protein level: Phosphorylation, ubiquitination and post translatational modifications that leads to protein degradation.
This process is way more complex than I said - for that I recommend the following articles:
http://www.ncbi.nlm.nih.gov/pubmed/11932736
http://www.hindawi.com/journals/tswj/2014/896206/
http://www.ncbi.nlm.nih.gov/pubmed/21802130
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