Q. Zhang et al., FUNCTIONAL AND PHYSICAL INTERACTION BETWEEN P53 AND BZLF1 - IMPLICATIONS FOR EPSTEIN-BARR-VIRUS LATENCY, Molecular and cellular biology, 14(3), 1994, pp. 1929-1938
The p53 tumor suppressor protein, which is commonly mutated in human c
ancers, has been shown to interact directly with virally encoded prote
ins from papillomavirus, adenovirus, and simian virus 40. The disrupti
on of p53 function may be required for efficient replication of certai
n viruses and may also play a role in the development of virally induc
ed malignancies. Infection with Epstein-Barr virus (EBV) has been asso
ciated with the development of B-cell lymphomas and nasopharyngeal car
cinoma. Here we show that the EBV immediate-early protein, BZLF1 (Z),
which is responsible for initiating the switch from latent to lytic in
fection, can interact directly in vitro and in vivo with the tumor sup
pressor protein, p53. This interaction requires the coiled-coil dimeri
zation domain of the Z protein and the carboxy-terminal portion of p53
. Overexpression of wild-type p53 inhibits the ability of Z to disrupt
viral latency. Likewise, Z inhibits p53-dependent transactivation in
lymphoid cells. The direct interaction between Z and p53 may play a ro
le in regulating the switch from latent to lytic viral infection.