Peptidylproline cis - trans -Isomerase Pin1 Interacts with Human T-Cell Leukemia Virus Type 1 Tax and Modulates Its Activation of NF-κB

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus etiologically causal of adult T-cell leukemia (ATL). The virus encodes a Tax oncoprotein that functions in transcriptional regulation, cell cycle control, and transformation. ATL is a highly virulent cancer that is resistant to chemotherapeutic treatments. To understand this disease better, it is important to comprehend how HTLV-1 promotes cellular growth and survival. Tax activation of NF-B is important for the proliferation and transformation of virus-infected cells. We show here that prolyl isomerase Pin1 is over expressed in HTLV-1 cell lines; Pin1 binds Tax and regulates Tax-induced NF-B activation.

Ubiquitin-Specific Peptidase 20 Targets TRAF6 and Human T Cell Leukemia Virus Type 1 Tax To Negatively Regulate NF-κB Signaling

“…Ubiquitination, sumoylation, acetylation, and phosphorylation of Tax have been shown to influence its transcriptional function (5,9,22,23,25,28,34,35,40). Tax ubiquitination has been reported to be required for its activation of NF-B, and it has been found that the Tax-polyubiquitin chains are predominantly K63 linked (40).…”

Peptidyl-Prolyl Isomerase Pin1 Is a Cellular Factor Required for Hepatitis C Virus Propagation

“…Among candidate genes, we selected and characterized the gene encoding Pin1, because it has been implicated in many viral infections, including human immunodeficiency virus (HIV) replication (29), HBV-mediated hepatocarcinogenesis (17), and human T cell leukemia virus type 1 (HTLV-1) malignant transformation (7,20). Silencing of Pin1 expression led to strong inhibition of HCV production (Fig.…”

“…It interacts with hepatitis B virus X protein to enhance hepatocarcinogenesis (17). Pin1 stabilizes human T cell leukemia virus type 1 (HTLV-1) Tax oncoprotein and promotes malignant transformation (7,20). Pin1 also modulates the replication of human immunodeficiency virus type 1 (HIV-1) via interaction with APOBEC3G protein (29).…”

TCF1 and LEF1 act as T-cell intrinsic HTLV-1 antagonists by targeting Tax

“…Expression vectors for TCF1, LEF1, and Tax were described (16,45). Flag-CREB was made by subcloning the CREB coding sequence into pCAGFlag.…”