Pin1 Interacts With a Specific Serine-Proline Motif of Hepatitis B Virus X-Protein to Enhance Hepatocarcinogenesis

Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein

“…As HBV replication in hydrodynamic mouse model and hepatocarcinogenesis in transgenic mice are promoted in the presence of HBx, it is plausible that these processes may be characterized by inhibition of innate immune response by HBx. In line with this notion, Pin1, which negatively regulates IRF3 signaling (Saitoh et al, 2006), is overexpressed prevalently in HBV-HCC positive for HBx (Pang et al, 2007). In addition, reduced CARDIF protein levels have been recently reported to correlate well with HBx expression in HBV-HCC (Wei et al, 2010).…”

The role of signaling pathways in the development and treatment of hepatocellular carcinoma

“…During chronic infection, HBV integrates into host DNA and expresses two transcriptional activators, both of which trigger activation of the RAF/MEK/ERK pathway (Stockl et al, 2003). The first activator, HBX protein, interacts with PIN1 (also overexpressed in HCC) (Pang et al, 2007), which may enhance activation of the MAPK pathway through dephosphorylation of CRAF, promoting its activation by RAS (Dougherty et al, 2005), whereas the second activator, PreS2-activator large surface protein, activates the pathway through a protein kinase C-dependent mechanism (Stockl et al, 2003). Note that we have previously shown that when CRAF is activated downstream of protein kinase C, it occurs in a RAS-dependent manner (Marais et al, 1998) and hence it seems likely that CRAF activation downstream of protein kinase C in HCC cells is also RAS dependent.…”

PI3-Kinase/p38 Kinase-Dependent E2F1 Activation Is Critical for Pin1 Induction in Tamoxifen-Resistant Breast Cancer Cells

“…Pin1 overexpression stimulates neoplastic transformation of non-tumorigenic hepatocyte and epidermal cell lines (Lee et al, 2009;Pang et al, 2007). Furthermore, Pin1 ablation is highly effective in preventing Neu-or HBx-enhanced tumor growth in mouse tumor models (Pang et al, 2007;Wulf et al, 2004). Hence, Pin1 may be an important mediator of the development of several types of cancers.…”