A Kaposi's sarcoma-associated herpesvirus protein that forms inhibitory complexes with type I interferon receptor subunits, Jak and STAT proteins, and blocks interferon-mediated signal transduction.

Type I interferons (IFNs) are important mediators of innate antiviral defense and function by activating a signaling pathway through their cognate type I receptor (IFNAR). Here we report that lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV) efficiently blocks type I IFN signaling and that an important effector of this blockade is the viral protein RIF, the product of open reading frame 10. RIF blocks IFN signaling by formation of inhibitory complexes that contain IFNAR subunits, the Janus kinases Jak1 and Tyk2, and the STAT2 transcription factor.

The phytochemical piceatannol induces the loss of CBL and CBL-associated proteins.

Piceatannol is a naturally occurring bioactive stilbene with documented antileukemic properties. It has been extensively used as a Syk-selective protein tyrosine kinase inhibitor for the study of various signaling pathways. Herein, we show that the hydroxystilbene, piceatannol, and related catechol ring-containing compounds are able to induce the loss of the Cbl family of proteins.

Isolation and characterization of a novel, transforming allele of the c-Cbl proto-oncogene from a murine macrophage cell line.

The c-Cbl proto-oncogene acts as an E3 ubiquitin ligase via its RING finger domain to negatively regulate activated cellular signal transduction pathways. We have identified an aberrant Cbl-protein of approximately 95 kDa, which we have called p95Cbl, from the murine reticulum sarcoma cell-line, J-774. Cloning of the p95Cbl cDNA revealed that it contains a deletion resulting in the loss of 111 amino acids, eliminating two critical tyrosine residues in the linker region as well as the entire RING finger domain.