The cell is what you imagine it to be: AKT an the FOXO Gang

AKT Review

What I read:

“Activated AKT is a well-established survival factor, exerting antiapoptotic activity in part by preventing the release of cytochrome c from the mitochondria. AKT also phophorylates and inactivates the proapoptotic factors BAD and procaspase-9. Moreover, AKT phosphorylates and inactivates the FOXO transcriptions factors, which mediate the expression of genes critical for apoptosis, such as the Fas ligand gene. AKT also inactivates IK kinase, a positive regulator of NF-kB, which results in the transcriptions of antiapoptotic genes. In another mechanism to thwart apoptosis, AKT promotes the phosphorylation and translocation of Mdm2 into the nucleus, where it downregulates p53 and thereby antagonizes p53-mediated cell cycle checkpoints.”

(This is what apoptosis looks like)
Apoptosis

What I imagine:

A lone protein stands for justice in the cell, delivering punishment to those who would destroy it with righteous fury. Any time a mitochondrial drug smuggling ring attempts a major operation to release a toxic agent into the cell, he is there, swinging with the iron fist of the law.

On a dark and cold night, AKT, perched high up in the Golgi, looks down and sees the nefarious duo BAD and P9. They are heading towards the self-destruct center of the cell! Acting quickly, our hero zip-lines down an actin filament and takes down the two trouble-makers.

“Please, have mercy AKT!” BAD pleas, his body disfigured from the conformational change brought about by AKT’s forceful phosphorylation.

With a grim look in his eyes, AKT says, “It’s off to the lysozome with you two! This cell with not be destroyed on my watch!”

Suddenly, AKT feels a shift in the cytoplasm. Someone is tampering with the Fas ligand gene in the nucleus! The whole cell could go apoptotic at any moment! AKT speeds to the nucleus, where he finds the FOXO gang at the final stages of transcribing the Fas ligand. “You’re too late AKT! The cell will be no more!”

“Not on my watch!” AKT ducks and rolls, then quickly slings several phosphate groups at the FOXO gang. They attempt to dodge, but AKT has impeccable aim. Lying gasping on the nuclear membrane, the FOXO gang leader, looks up at AKT. “You’re … too … late!” He then shakily points his finger at the Fas ligand mRNA being transported out of the cell.

“Cancer!” AKT curses. Then, acting quickly, he runs to a nearby chromosome. IK kinase is hanging around, watching the swirling eddies in the cytoplasm, when AKT phosphorylates him from behind. “I’m sorry, but it was necessary.” He then looks at IK kinases’ underling, NF-kB, who takes one glance at the furious expression on AKT’s face and scurries away. A polymerase then swoops in and begins transcribing AKT’s sidekick, and AKT leaves instruction for him to take care of the errant Fas ligand. Then, as another precaution, AKT beckons Mdm2 into the nucleus and gives instruction for p53 to be lackadaisical on the next few checkpoints.

Wearied but triumphant, AKT returns to his perch on the Golgi, watching against those agents of destruction. The cell buzzes with activity below him, secure in the knowledge that he is there, waiting, watching, protecting.

_______________________

I wrote this a long while ago while reading up on AKT.  AKT is at the the head of one of the most important signalling pathways in the cell, as it regulates apoptosis.  In the story above, he is flouting various proteins from initiating programmed cellular death – apoptosis.  He is depicted as a hero, but in actuality, when AKT is mutated and doesn’t allow a cell that should die to die, the cell can continue to grow and divide with the mutation, leading to cancer.  That is why AKT is one of the most studied oncogenes in cancer.

Hope you enjoyed the story!

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