TY - JOUR
T1 - An N-terminal arginine-rich cluster and a proline-alanine-threonine repeat region determine the cellular localization of the herpes simplex virus type 1 ICP34.5 protein and its ligand, protein phosphatase 1
AU - Mao, Hanwen
AU - Rosenthal, Kenneth S.
PY - 2002/3/29
Y1 - 2002/3/29
N2 - The ICP34.5 protein facilitates herpes simplex virus replication by binding and activating protein phosphatase 1 (PP1) by means of a very conserved C-terminal GADD34-like region. Natural variants of the ICP34.5 differing in the number of arginines in an Arg-rich cluster at the N terminus and the number of Pro-Ala-Thr repeats in the central bridge region of the protein were cloned as fusion proteins with a reporter peptide (c-Myc or hrGFP) at the C terminus. The natural variants were obtained from strains differing in passage history, tissue culture behavior, and neuroinvasive disease potential. In transfected cells, these variants localized to different subcellular compartments. The N-terminal Arg-rich cluster acted as a cellular localization signal for discrete regions of the nucleus and cytoplasm, but the ultimate location of ICP34.5 was determined by the number of Pro-Ala-Thr repeats in the central bridge region. PP1 colocalized with the ICP34.5 variant in cells expressing the ICP34.5. The ICP34.5-mediated, herpes simplex virus strain-dependent differences in the modulation of PP1 location and function may be responsible for the strain-associated differences in tissue culture behavior and virulence of the virus.
AB - The ICP34.5 protein facilitates herpes simplex virus replication by binding and activating protein phosphatase 1 (PP1) by means of a very conserved C-terminal GADD34-like region. Natural variants of the ICP34.5 differing in the number of arginines in an Arg-rich cluster at the N terminus and the number of Pro-Ala-Thr repeats in the central bridge region of the protein were cloned as fusion proteins with a reporter peptide (c-Myc or hrGFP) at the C terminus. The natural variants were obtained from strains differing in passage history, tissue culture behavior, and neuroinvasive disease potential. In transfected cells, these variants localized to different subcellular compartments. The N-terminal Arg-rich cluster acted as a cellular localization signal for discrete regions of the nucleus and cytoplasm, but the ultimate location of ICP34.5 was determined by the number of Pro-Ala-Thr repeats in the central bridge region. PP1 colocalized with the ICP34.5 variant in cells expressing the ICP34.5. The ICP34.5-mediated, herpes simplex virus strain-dependent differences in the modulation of PP1 location and function may be responsible for the strain-associated differences in tissue culture behavior and virulence of the virus.
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U2 - 10.1074/jbc.M111553200
DO - 10.1074/jbc.M111553200
M3 - Article
C2 - 11788604
AN - SCOPUS:0037192835
SN - 0021-9258
VL - 277
SP - 11423
EP - 11431
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 13
ER -