Furthering characterization of human HERC5: A novel member of the antiviral response

HERC5 was initially characterized as a protein capable of binding to cyclins, a family of cell cycle-associated proteins. Further investigations into the transcriptional regulation of HERC5 demonstrate that it is responsive to viral infection and oncogenic transformation. Research presented here provides direct evidence that HERC5 is an interferon-responsive gene, and is in fact directly transcriptionally activated following stimulation of the type I interferon receptor. HERC5 is also stimulated by a double-stranded RNA responsive pathway, and while this activation displays delayed kinetics, it also demonstrates a much greater transcriptional induction. Furthermore, findings presented here draw into question the role of HERC5's putative interaction with cyclins, as their localization appears to be independent of one another. Finally, a role for HERC5 in modulating the cytoskeleton and/or cell cycle factors is proposed, subsequent to demonstrating that ectopic expression of HERC5 in U-2 OS cells induces nuclear dysmorphisms reminiscent of mitotic catastrophe.