Thursday, January 30, 2014

New Challenges to the human cell

In a world where new stimulants and new conditions are created, the human cell, deep in our systems, is confronted and forced to adapt and conform to new environment constantly. And doing so with the human genes that it possesses at the moment.  Yes, while a chemist work hard to create new chemical product to improve our lives (I really hope this), the cell somewhere in the human body does not know it will face this new challenge once it comes to contact with it.  To deal with this new product as a stimulant, the cell has to use its potentials.  It has sometime to rearrange its mechanisms to deal with the new stimulant!  While most of the time quick adaptation to the new product is limited in its impact on the life of the cell, certain stimulants will lead to receptor desensitization, transcription factors amplifications (particularly if gene autophosphorylation is allowed, shutdown of regulators occurs, alteration in splicing, and special miRNA are transcribed,etc.).  The point is even Receptor desensitization itself may lead to shutdown of critical genes.
One of the things that makes the cell vulnerable to the effect of new stimulant, is not only its reliance to old techniques to fight new challenges (ie, activation of the NF-kB) but also proximity and interactivity of the genes particularly those in the proximity of the initial inducing events.  But in a lightening fast action, distant genes are also involved.  The proximity of basic cellular functions is also a player.  Indeed it is common that one event could affect various cellular functions such as proliferation,growth and differentiation.  In fact the ease of recruiting neighbor gene is impressive.  It does not take much for a stimulant to induce de-differentiation to return cellular omnipotence to deal with the new comer, but cellular omnipotence is sitting next to shutting Apoptosis so that the new challenge does not kill the cell, But as seen in many cases, gene repair mechanisms are raised to the ready (in some cases shut down to tolerate mistakes), splicing machines are set  in motion to make new RNA to create adapted novel proteins, multiplication machinery are also ready to clone resistant cells, messaging machinery is put in a "work" mode to notify surrounding cells in case they don't know already.   The most sensitive function of all is the machinery to induce JAK/STAT and the variable domain of immunoglobulins.  Once these are engaged, a potential neoplastic transformation is possible if attachment to the involved gene occurs!

An example of this is what happen in Hodgkin disease, if you read about PAX genes, you will find cellular de-differentiation, PAX1-engage MOX1 but surprise-surprise-BRCA1 is not far.   You will argue that PAX5 is the one in 97% of some Hodgkin Lymphomas, but follow the TLE4,  Daxx, AML1,TATA,and RAG1....you will find that the same story repeats itself!

The CRBCM is following the trail!
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