G(0) G(1), GROWTH ARREST MEDIATED BY A REGION ENCOMPASSING THE BASIC LEUCINE-ZIPPER (BZIP) DOMAIN OF THE EPSTEIN-BARR-VIRUS TRANSACTIVATOR ZTA/

The Epstein-Barr virus (EBV) immediate early transactivator Zta is a b asic leucine zipper (bZIP) transcription factor that causes G(0)/G(1) cell cycle arrest through induction of the tumor suppressor protein, p 53, and the cyclin-dependent kinase inhibitors, p21 and p27 (Cayrol, C ., and Flemington, E. K. (1996) EMBO J. 15, 2748-2759). Here, we repor t a genetic analysis of Zta-mediated G(0)/G(1) growth arrest and p21 i nduction. The majority of the Zta transactivation domain can be delete d (Z Delta 1-128) without significantly affecting the ability of Zta t o elicit growth arrest. A larger amino-terminal deletion (Z Delta 1-16 7) abrogates the ability of Zta to inhibit proliferation, mapping the growth-inhibitory domain to a carboxyl-terminal region encompassing th e bZIP domain (amino acids 128-245), The integrity of the bZIP domain is required for growth suppression since a two-amino acid mutant which is defective for homodimerization, fails to induce cell cycle arrest. Western blot analysis of p21 expression in cells expressing Zta mutan ts reveals that the ability of Zta mutants to cause G(0)/G(1) growth a rrest is intimately related to their capacity to induce p21 expression . Together, these data demonstrate that a carboxyl-terminal region of Zta that includes the bZIP domain is sufficient to mediate G(0)/G(1) g rowth arrest and p21 induction.