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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Latency Abstract 5
INTERACTION OF KSHV LANA-1 WITH USP7: IMPLICATIONS FOR P53
FUNCTION
W. Albrecht (1), E. Gellermann (1), A. Viejo-Borbolla (2), T. F. Schulz (1)
(1) Institute of Virology, Hanover Medical School, Hanover, Germany
(2) Dept. of Cell and Molecular Biology, Centro Nacional de Biotecnología, Madrid, Spain
Abstract
LANA-1 is constitutively expressed in all latently KSHV-infected cells and displays several
functions in the persistence and replication of the viral episome.
We found the ubiquitin-specific protease 7 (USP7) to be a new interaction partner of
LANA-1. USP7 was originally identified in association with the HSV-1 protein ICP0, an E3
ligase, and is thought to prevent the proteasomal degradation of autoubiquitinated ICP0.
The EBV EBNA-1 protein, which is functionally related to LANA-1, also recruits USP7 and
is thought to absorb USP7 from p53, one of its physiological targets, thereby leading to
the destabilization of p53.
USP7 binds to LANA-1 via a sequence motif resembling the USP7-binding site in EBNA-1.
However, LANA-1 mutants lacking this binding site were not compromised in their ability
to antagonize p53-mediated transcriptional activation. LANA-1 interacts directly with p53
and we mapped the binding site to three amino acids in the C-terminus of LANA-1.
Mutation of the p53-binding site eliminates the ability of LANA-1 to antagonize p53dependent
transcriptional activation.
Furthermore, LANA-1 mutants lacking the USP7-binding site showed evidence of
increased ubiquitination.
These findings indicate that the model of p53 stabilization by ‚squelching‘ of USP7, as
developed for EBNA-1, does not apply to LANA-1 and that direct binding of p53 to
LANA-1 is required for its ability to antagonize p53 function. In contrast, binding of USP7
by LANA-1 may modulate ubiquitination of LANA-1.
We currently investigate the functional importance of LANA-1 ubiquitination and the
properties of LANA-1 mutants deficient in USP7 binding.
Presenting author Email: albrecht.wiebke@mh-hannover.de
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Comment [W1]: ?
Comment [W2]: ?