Saturday, December 15, 2012

AT A CHECK POINT IN CELL DIVISION 2 MAIN THINGS HAPPEN:

1. DNA is checked for mistakes and corrections are undertaken.2. Chromosome segregation to eventual daughter cells is checked to avoid uneven distribution of the chromosome. 
This last event seems to rely heavily on activity on unattached chinetochores where check point proteins (MAS 1 & 2, UB1 etc.) accumulate and block the APX (Anaphase promoting complex) until the checking is completed and Cyclin B and Securins are ubiquitinated and destroyed to release the check hold and allow mitosis to proceed.

The need for ubiquitination of Cyclin B elevate the role of Proteasome. That is why Antiproteasome appears very important in hematologic conditions where signal transduction and subsequent cyclin activity are the driving forces toward multiplictaion of cancer cells as we stated.

When all this is  going on, the cancer cell is at its weak point. That is why chemotherapy, particularly the Taxanes and the Vinca-alkaloids, is more effective. It not only disturbs the microtubule (inducing the 2nd law), but also breaks the actinic anchors to the cytoskeleton of membranes and cellular matrix causing the "Anoikis" like phenomenon within the cell. Lesion to actin like molecules (anchors) within the central nervous system could lead to neuropathy. As we know it has the side effect of these drugs (proof of concept to follow).

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