Regulation of Cell Proliferation Oncogenes

Apoptosis (programmed cell death) is characterized by a complex series of biochemical changes that culminate in cell death without inflammation or swelling, which are signs of necrosis. Embryonic, fetal, and postnatal development involve cell death by apoptosis, which serves to eliminate excessive cell proliferation and migration. Apoptosis is initiated by a variety of external stimuli and molecular events such as oxidative stress, mitochondrial permeability transition, mitochondrial cytochrome c release, activation of caspase proteases, activation of endonucleases, transglutaminase activation, and poly(ADP-ribose) polymerase cleavage. 

ALS was first described by the French neurologist Chariot in 1869. The disease involves rapid loss of motor neurons in the cortex, brain stem, and spinal cord death usually follows 3-5 years after diagnosis. ALS is more commonly referred to as Lou Gehrig s disease because it struck down the New York Yankees immortal at the peak of his baseball career. ALS usually occurs in a sporadic form but in rare cases there is a familial factor this provided the first clues to the molecular basis for ALS. 

The first oncogene discovered was src, a gene carried by Rous sarcoma virus that causes sarcomas in infected fowl. 

Genome of the Rous sarcoma virus (RSV). The single-stranded RNA is about 10 kb. Four proteins are encoded in this retrovirus gag, a core protein pol, reverse transcriptase env, glycoprotein of the envelope and src, a nonessential viral gene whose product is responsible for cellular transformation. LTR, Long terminal repeat sequences present at the ends of each viral RNA molecule. 

The normal ras p21 binds GTP and GDP it also hydrolyzes GTP to GDP. The mutant ras p21 proteins show reduced or complete absence of GTPase activity. In this regard, normal p21 appears to be similar to the cellular G (GTP-binding) protein that activates adenylate cyclase and thereby mediates cellular activities. 

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