Inhibition of 12-O-tetradecanoylphorbol-13-acetate induction of c-fos mRNA by the protein kinase A inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide

Huang, Ying-Tang; Lin, Jen‐Kun; Lee, Ming-Ting

doi:10.1016/s0006-2952(99)00238-5

Cited by 3 publications

(1 citation statement)

References 49 publications

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“…The aforementioned CBP, as well as p300, are transcriptional coactivators with intrinsic histone acetyltransferase (HAT) activity that bind to Rta at downstream Rta target promoters [ 7 , 37 , 52 ]. AP-1 is a complex of c-Jun and c-Fos proteins and may contribute the strongest transactivation activity for Rta expression, as evidenced by induction of a productive replication cycle by TPA that is similar to Rta-mediated induction [ 2 , 4 , 7 , 14 , 79 , 81 , 93 ]. Signal transducer and activator of transcription 3 (STAT3), a growth factor- and cytokine-responsive regulator, is dimerized by Rta, allowing STAT3 to translocate to the nucleus and induce STAT3 transcriptional targets [ 94 ].…”

Section: Function and Regulation Of Rta Lytic Switch Proteinmentioning

confidence: 99%

KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control

Guito

Lukac

2015

Viruses

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In Kaposi’s sarcoma-associated herpesvirus (KSHV) oncogenesis, both latency and reactivation are hypothesized to potentiate tumor growth. The KSHV Rta protein is the lytic switch for reactivation. Rta transactivates essential genes via interactions with cofactors such as the cellular RBP-Jk and Oct-1 proteins, and the viral Mta protein. Given that robust viral reactivation would facilitate antiviral responses and culminate in host cell lysis, regulation of Rta’s expression and function is a major determinant of the latent-lytic balance and the fate of infected cells. Our lab recently showed that Rta transactivation requires the cellular peptidyl-prolyl cis/trans isomerase Pin1. Our data suggest that proline‑directed phosphorylation regulates Rta by licensing binding to Pin1. Despite Pin1’s ability to stimulate Rta transactivation, unchecked Pin1 activity inhibited virus production. Dysregulation of Pin1 is implicated in human cancers, and KSHV is the latest virus known to co-opt Pin1 function. We propose that Pin1 is a molecular timer that can regulate the balance between viral lytic gene expression and host cell lysis. Intriguing scenarios for Pin1’s underlying activities, and the potential broader significance for isomerization of Rta and reactivation, are highlighted.

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