The amino-terminus and membrane-spanning domains of LMP-1 inhibit cell proliferation

The LMP-I oncoprotein of EBV is required to maintain proliferation of infec ted B-cells and shares several features with CD40, TNF-R1, and related rece ptors, Members of this family can bind TRAF and TRADD molecules and activat e NF-kappa B and AP-I, as can LMP-1, While CD40 and TNF-R1 are dependent on binding their ligands for their signaling, LMP-1 apparently is not, We hav e found that LMP-1 can act as a governor of cell proliferation and thereby limit its own activities, its inhibition of proliferation is not mediated b y apoptosis but results in cytostasis in four cell lines tested. The struct ural moiety of LMP-I that distinguishes it from CD40 and TNF-R1, its amino- terminus and multiple membrane spanning segments, alone can mediate its cyt ostatic activity.