|Kung, Hsing-Jien - CASE WESTER RESERVE UNIV|
|Liu, Juinn-Lin - CASE WESTERN RESERVE UNIV|
Submitted to: EMBO Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 1, 1998
Publication Date: N/A
Interpretive Summary: Marek's disease remains a major problem in the commercial poultry industry. The purpose of this research was to demonstrate that MEQ, a Marek's disease virus gene, resembles another gene family with the property of inducing tumors. We found MEQ product is abundantly produced in Marek's disease virus tumor cell lines. We also found the association of MEQ product with another product (CDK2) produced by normal cells for control of cell growth This report is the first evidence that a Marek's disease virus MEQ gene may be interfering with normal cell growth and thus cause cancer in chickens. This knowledge will help us design and alter Marek's disease virus so that it will not cause tumor in chickens. Success here would have a tremendous impact on the poultry industry by reducing losses due to Marek's disease.
Technical Abstract: This is the first demonstration that CDK2 is found to localize to the coiled bodies. Such an in vivo association and possibly subsequent phosphorylation may result in the cytoplasmic translocation of MEQ protein. Indeed, MEQ is expressed in both the nucleus and the cytoplasm during the phase. In addition, we were able to show in vitro phosphorylation of MEQ by CDKs. An indirect immunofluorescence study of MEQ mutant, S42D, in which the CDK phosphorylation site was mutated to a charged residue, reveals more prominent cytoplasmic localization. This leads further support to the notion that MEQ's translocation is regulated by phosphorylation. Furthermore, phosphorylation of MEQ by CDKs drastically reduces the DNA-binding activity of MEQ, which may in part account for the lack of retention of MEQ oncoprotein in the nucleus. Interestingly, the localization of CDK2 to the coiled bodies and the nucleolar periphery is observed only in MEQ-transformed Rat-2 cells, implicating MEQ in modifying the subcellular localization of CDK2. Taken together, our data suggest that there is a novel reciprocal modulation between the herpesviral oncoprotein MEQ, and CDK2.