Plegable UPB Biomol

The DNA’s repplication and gene expression needs relaxed histones. The Acetyl-coA group allowed this, but Its nucleus process was unknown.

The two more common illnesses from old ages: Cancer and neurodegeneration are related.

New way foundby which metabolism is linked to the regulation of DNA


SCIENCE DAILY (July 4th 2014)



SCIENCE DAILY

(July 4th 2014)

- The Pyruvate dehydrogenase complex is a mitochondrial enzyme which catalyzes the pyruvate from the Glycolisis into an acetyl CoA molecule, Subsequent it goes to krebs cycle and by a mitochondrial way, is used by the histones to unwind the DNA for its repplication an expression of the genes.

-The Pyruvate dehydrogenase complex (PDC) was thought always it reside only within mitochondria, but due this research they found that it can actually find its way into the nucleus and do what it is designed to do in the mitochondria: generate acetyl-CoA .

-The researchers were measuring PDC levels at mitochondria but accidentaly they also found its levels at the cell nucleus.



-At mitochondria PDC generates acetyl- CoA for energy production

-At nucleus PDC generates acetyl-Coa for histone acetylation

-They discovered an other way this enzyme works inside the cells and also found that it accelerates the growing of cancer cells



SCIENCE DAILY

(July 29 2014)

Discovery of a pro-metastasis protein

reveals misterious link to neurodegeneration







-Scientists have discovered a protein that activates the motion of metastasis in patients with cancer and also it has the characteristic of inhibit genes related with neurodegeneration.

They scaned RNA’s sequences of the tumoral breast cells and discovered on their RNA’s shapes binding sites for proteins that set the path of the destructive molecule.





-Following these paths they found many hairpins with the RNA target for destruction, and inside of them found a protein which they named “ TARBP2”.

-Later on they investigated which genes were affected and found: APP gene associated with alzheimerZNF395 associated with huntington’s disease

So the TARBP2 apparently turns off the action of these genes

TARBP2

APP





Finally they discovered something else:

The APP and ZNF395 were not that bad all: they were implied on avoid cancer’s spread by metastasis and its gene exppresion.

APP GENEZNF395GENE

TARBP2

New way foundby which metabolism is linked

to the regulation of DNA





The discovering of the presence of PDC at cell nucleus allows the join with cancer’s intracellular action mechanism due its relation with DNA replication and gene expression in which both have an important role

It generates better depth study about the molecular processes occurring and the possibility of discovering/creating new ways of treatment/prevention by genetic terapy

Discovery of a pro-metastasis proteinreveals misterious link to neurodegeneration


TARBP2 and its relation with the inhibition of tumor suppressor genes, allowed to discover more mechanisms of action of cancer and the group of implied genes. Knowing the ones affected there could be designed a way to protect them against the damage.



Given the potential action of APP and ZNF395 genes (associated with Alzheimer + decreases metastasis of breast cancer and associated with huntington’s disease + decreases cancer’s genes), there can begin to make gene therapy in patients with these diseases and begin investigating ways in the pharmaceutical field to find preventive and therapeutic action against their damage by cancer or inhibit their neurodegenerative action.

• Sutendra, G. A Nuclear Pyruvate Dehydrogenase Complex Is Important for the Generation of Acetyl-CoA and Histone Acetylation. Cell Magazine, 2014; 158 (1): 84

• Goodarzi, H. Zhang, S. Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins. Nature Magazine, 2014; DOI: 10.1038

• Martinez, Lina. Biologia Molecular. 4. ed. Medellin: UPB. Facultad de medicina. 2008. 286p

Education

Plegable UPB Biomol