Expression of interferon-stimulated gene ISG15 and ubiquitination enzymes is upregulated in peripheral blood monocyte during early pregnancy in dairy cattle

Peer Review #2 of "Comparative proteome analysis reveals VPS28 regulates milk fat synthesis through ubiquitylation in bovine mammary epithelial cells (v0.1)"

“…Following VPS28 knockdown, proteasome activity and the expression of ISG15 (interferon-stimulatory gene ISG15) were decreased. ISG15 is an ubiquitin-like protein that mediates the conjugation of different proteins through its ISGylation enzymes UBE2L6 (ubiquitin conjugating enzyme E2 L6)(19), and we also found UBE2L6 was down regulated. Previous studies have suggested that down-regulation of ISG15 and UBE2L6 can counteract degradation of triglyceride lipase(20)(21)(22), and ISG15…”

Molecular cloning and expression kinetics of serum interferon stimulated gene for early pregnancy detection

“…The detection of ISG15 mRNA has yielded 78% accuracy in predicting pregnant cows, while progesterone only has yielded 58% accuracy (Han et al, 2006). Recently, it has been reported that the secretion of IFN-t by the conceptus acts on PBMCs to upregulate the interferon-stimulated gene (ISG15) an ubiquitin-like protein that mediates the conjugation of different proteins through its ISGylation enzymes UBE1L and UBCH8 ( Austin et al, 2004;Haq et al, 2016). In the context of the above experiments, RNA was collected from the animal blood on day 18 of pregnancy and cDNA was amplified using primers specific to the coding region of ISG15.…”

Changes in expression of interferon-stimulated genes and ubiquitin activating enzyme E1-like in ovine thymus during early pregnancy

“…UBE1L is a core E1 enzyme for ISG15 conjugation (ISGylation) that ISG15 conjugation to a target protein is not for target protein degradation, but involved in regulating the function of the target protein (Durfee and Huibregtse, 2010). Expression of UBE1L protein is increased in the uterus during early pregnancy in cows (Rempel et al, 2005), and early pregnancy induces upregulation of UBE1L genes in bovine PBMCs (Haq et al, 2016). ISGylation participates in the innate immunity, but fertile ability and antiviral responses is normal in a mouse model deficient in UBE1L, suggesting that UBE1L and protein ISGylation are not necessary for type 1 interferon signaling (Kim et al, 2006).…”

“…ISGs play key roles in the antiviral response of the host, and are required for the innate immune system (Hubel et al, 2019). Ubiquitin activating enzyme E1-like protein (UBE1L) participates in ISG15 conjugation, and ISG15 and UBE1L mRNA increase in peripheral blood mononuclear cells (PBMCs) on day 18 of pregnancy in cows (Haq et al, 2016). UBE1L is involved in modulation of protein functions through covalent attachment of ubiquitin or ubiquitin-like proteins (Ebner et al, 2017).…”