Tuesday, April 2, 2013

CRITICAL GENES IN (SECONDARY) LEUKEMIA

Aside from the the genes that can block Tumor Growth factors, our discussion on leukemia had shown that Leukemia is driven also by proteins located at CBF.  Indeed we now know that the proteins found in the CBF indeed determine the direction and intensity of the the neoplastic process.  Attacking growth factors effectiveness at stimulating its relevant receptor appears to be a decent strategy.   However there are other gene that should be in the focus of our attention.
AP-1
TFE-3
SMAD2-4
FOXG1
and at the border JARID1B
(we will add some gene regulators to this list)
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'"The SMAD4 gene provides instructions for making a protein involved in transmitting chemical signals from the cell surface to the nucleus. This signaling pathway, called the transforming growth factor beta (TGF-β) pathway, allows the environment outside the cell to affect how the cell produces other proteins. The signaling process begins when a TGF-β protein attaches (binds) to a receptor on the cell surface, which activates a group of related SMAD proteins. The SMAD proteins bind to the SMAD4 protein and form a protein complex, which then moves to the cell nucleus. In the nucleus, the SMAD protein complex binds to specific areas of DNA where it controls the activity of particular genes and regulates cell growth and division (proliferation).
By controlling gene activity and regulating cell proliferation, the SMAD4 protein serves both as a transcription factor and as a tumor suppressor. Transcription factors help control the activity of particular genes, and tumor suppressors keep cells from growing and dividing too fast or in an uncontrolled way.

Does the SMAD4 gene share characteristics with other genes?

"The SMAD4 gene belongs to a family of genes called SMAD (SMAD, mothers against DPP homologs).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? in the Handbook."  
 "Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for syngernistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator."
(NIH)

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