ASKl(apoptosis signal-regulating kinase 1) is an important mediator of a poptotic s ignaling initi ated by a variety of death stimuli, including tumor necrosis factor ‘ Fas activat ion, oxidative st ress, and DNA damage. It was originally discovered as a mitogen -activated protein kinase kinase kinase(MAP3K) with proapoptotic activ ity Wben the A8Kl is stimulated, it activates both the MKK4/MKK7-JNK pathway and the M와(3/MKK6- p38 ki nase pathway‘ leading to stress responses or apoptosis. Owing to its critical role in promoting apoptosis. ASKl activity is highly control led in cells by multiple mechanisrns, includ ing phos ph이 ylation ， oligomeri zation, and protein protein inte ractions. Phosphorylation of A8Kl at Thr-845 has been correlated with its acti vation . while phos phorylation at 8er-83 by Akt/protein kinase B attenuates A8Kl activity . It has also been demonst rated that in tramol ecular interaction, probably between the NH2• terminal and COOH-terminal domains of ASKl, may be required to maintain A8Kl in its inactive state, whereas oligomeri zation of its COOH- terminal domains is correlated with ASKl activation. The most commonly observed means of ASKl regulation, however, is thrO\땅h protein-protein in teractions. Numerous proteins have been shown to bind ASKl to exert theiJ‘ reg버atory function. For example. binding of TRAF2 0 1' Daxx promotes ASK1 funct ion, whereas the kinase and proapoptotic activities of A8Kl a re inhibited by many other associated proteins, including reduced t hi oredoxin, glutaredoxin, Cdc25A‘ Hsp 72, A8Kl - in teracting protein 1. and 14-3-3 proteins. A novel mechan ism of the anti-apoptotic action of Raf-l via phys ical interaction with ASKl wi ll be described. Furthermore, signifi cance of phosphorylati on s ite of 8er-1034 in the C-terminal regula tory domain of A8Klin the apoptotic activity wil l be discussed

• Hae Ryoun Park(Depatment of Oral & Maxilfofaciaf Pathoiogy, college of Dentistry, Pusan Nationaf University)