Distinct p53, p53:LANA, and LANA complexes in Kaposi's Sarcoma--associated Herpesvirus Lymphomas.
The role of p53 in primary effusion lymphoma (PEL) is complicated. The latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) binds p53. Despite this interaction, we had found that p53 was functional in PEL, i.e., able to induce apoptosis in response to DNA damage (C. E. Petre, S. H. Sin, and D. P. Dittmer, J. Virol. 81:1912-1922, 2007), and that hdm2 was overexpressed. To further elucidate the relationship between LANA, p53, and hdm2, we purified LANA complexes from PEL by column chromatography. This confirmed that LANA bound p53. However, the LANA:p53 complexes were a minority compared to hdm2:p53 and p53:p53 complexes. The half-life of p53 was not extended, which is in contrast to the half-life of simian virus 40 T antigen-transformed cells. p53:p53, LANA:p53, and LANA:LANA complexes coexisted in PEL, and each protein was able to bind to its cognate DNA element. These data suggest that under normal conditions, p53 is inactive in PEL, thus allowing for exponential growth, but that this inactivation is driven by the relative stoichiometries of LANA, hdm2, and p53. If p53 is activated by DNA damage or nutlin-3a, the complex falls apart easily, and p53 exercises its role as guardian of the genome.
Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, Center for AIDS Research, University of North Carolina at Chapel Hill, CB no. 7290, 715 Mary Ellen Jones Bldg., Chapel Hill, NC 27599-7290, USA.
Wuguo
W
Chen
Isaac B
IB
Hilton
Michelle R
MR
Staudt
Christin E
CE
Burd
Dirk P
DP
Dittmer
D000956:Antigens, Viral / Q000302:isolation & purification / Q000378:metabolism*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D006566:Herpesviridae Infections / Q000150:complications* / Q000473:pathology* / Q000821:virology; D019288:Herpesvirus 8, Human / Q000302:isolation & purification*; D006801:Humans; D054685:Lymphoma, Primary Effusion / Q000473:pathology* / Q000821:virology*; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D016159:Tumor Suppressor Protein p53 / Q000302:isolation & purification / Q000378:metabolism*
D000956:Antigens, Viral; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; C109540:latency-associated nuclear antigen