ZAK has been implicated in cell cycle arrest regulation through its function on decreasing cyclin E expression. To explore the mechanistic basis for this regulation, the yeast two-hybrid system was used with a novel Krappel-type C2H2 zinc finger member cloned. This cloned cDNA encodes a novel protein with Kruppel-type zinc fingers designed as ZZaPK (zinc finger and ZAK associated protein with KRAB domain) and is widely expressed. ZZaPK, when it is expressed in cells, is growth promoted and might lead to increasing E2F expression and induce cyclin E/CDK2 activity, which counteracts the ZAK function. The model proposed here is that ZAK might play a role as an upstream signal to suppress the ZZaPK function and decrease E2F expression. (C) 2002 Elsevier Science (USA). All rights reserved.