The cardiac cell cycle, pocket proteins, and p300

Identification of cell cycle regulators—tumor suppressor “pocket” proteins, cyclins, cyclin-dependent protein kinases (cdks), and an emerging family of cdk inhibitors—has fueled fundamental research into mechanisms that regulate cell proliferation, as well as clinical investigation in the settings, especially, of cancer and restenosis. The failure of ventricular myocytes to regenerate through cell proliferation following infarction might arguably best be viewed as the ultimate problem in growth control, though until recently, only sporadic studies were available that addressed the identity or function of proteins governing the cell cycle in ventricular muscle. From this perspective, it may be less fruitful to debate whether mitoses never occur in adult ventricular muscle or merely do so with such rarity as to be inconsequential, than to define the repertoire of molecules that hold the cardiac cell cycle in check. To substantiate their operation in cardiac cells is the prerequisite step toward establishing what role such pathways might play in cardiac myogenesis, organogenesis, and pathophysiology.