Stephen Goodbourn

Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures.

IP: 54.70.40.11 On: Sat, 15 Dec 2018 21:37:32 Journal of General Virology (2000), 81, 2341–2364. Printed in Great Britain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

STAT1 Is Inactivated by a Caspase

Apoptosis involves the activation of a cascade of interleukin-1β converting enzyme-like proteases (caspases), a group of cysteine proteases related to the prototype interleukin-1β-converting enzyme (caspase-1). These proteases cleave specific intracellular targets such as poly(ADP-ribose) polymerase, DNA-dependent protein kinase, and nuclear lamins. We show here that apoptosis can be induced by double-stranded RNA. The induction of apoptosis by double-stranded RNA and other agents leads to the cleavage by a caspase of the signal transducer and activator of transcription factor, STAT1 which is pivotal in the signal transduction pathways of the interferons and many other cytokines and growth factors. The product of this cleavage is no longer able to mediate interferon-activated signal transduction and the cleavage event may play a role in regulating the apoptosis response itself.

Transcriptional activation by the human herpesvirus-8-encoded interferon regulatory factor

Human herpesvirus-8 (HHV-8), a gammaherpesvirus that is thought to be the viral aetiologic agent of Kaposis sarcoma and primary effusion lymphoma, encodes a homologue to cellular interferon regulatory factors (IRFs). The HHV-8 IRF homologue (vIRF; ORF K9) has previously been shown to inhibit gene induction by interferons and IRF-1 and to transform NIH3T3 cells or Rat-1 cells. Additionally, expression of antisense to vIRF in BCBL-1 cells results in the repression of certain HHV-8 genes, suggesting that vIRF may also positively regulate gene expression. We demonstrate that vIRF activates transcription when directed to DNA by the GAL4 DNA-binding domain. GAL-vIRF truncation constructs that individually are incapable of activating transcription can cooperate in transactivation when coexpressed in HeLa cells, suggesting that multiple regions of vIRF are involved in transactivation. These studies broaden the potential mechanisms of action of vIRF to include transcriptional activation as well as transcriptional repression.

T-Cell Activation: Transcriptional regulation in activated T cells

Assembly of the activated T-cell transcription factor, NF-AT, from two different types of subunit is sensitive to immunosuppressive drugs and is a striking example of gene regulation by convergent intracellular signals.