THE CARDIAC CELL-CYCLE, POCKET PROTEINS, AND P300

Identification of cell cycle regulators-tumor suppressor ''pocket'' pr oteins, cyclins, cyclin-dependent protein kinases (cdks), and an emerg ing family of cdk inhibitors-has fueled fundamental research into mech anisms that regulate cell proliferation, as well as clinical investiga tion in the settings, especially, of cancer and restenosis. The failur e of ventricular myocytes to regenerate through cell proliferation fol lowing infarction might arguably best be viewed as the ultimate proble m in growth control, though until recently, only sporadic studies were available that addressed the identity or function of proteins governi ng the cell cycle in ventricular muscle. From this perspective, it may be less fruitful to debate whether mitoses never occur in adult ventr icular muscle or merely do so with such rarity as to be inconsequentia l, than to define the repertoire of molecules that hold the cardiac ce ll cycle in check. To substantiate their operation in cardiac cells is the prerequisite step toward establishing what role such pathways mig ht play in cardiac myogenesis, organogenesis, and pathophysiology.