The adeno-associated virus Rep proteins target PP4:SMEK1 by preventing substrate recruitment - PubMed
a day ago
- #viral-host interaction
- #phosphatase regulation
- #AAV replication
- The study identifies the PP4:SMEK1/2 phosphatase complex as a regulator of wild-type AAV replication.
- AAV Rep68 interferes with substrate recruitment to PP4:SMEK1, leading to hyperphosphorylation of PP4 substrates KAP1S824 and RPA2S4/8/33, enhancing viral gene expression and replication.
- A direct interaction between KAP1 and SMEK1 is mediated by a MAPP short linear motif binding the SMEK1 EVH1 domain.
- A multifunctional complex involving PP4:SMEK1 and PP1:NIPP1 contributes to KAP1S824 dephosphorylation.
- The findings reveal a novel viral mechanism to subvert host phosphatases, advancing understanding of AAV and phosphatase biology, and potentially improving AAV vector potency.