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Activation of Notch1 signaling by HTLV-1 Tax promotes proliferation of adult T-cell leukemia cells

Cheng, Wenzhao, Zheng, Tingjin, Wang, Yong, Cai, Kun, Wu, Wencai, Zhao, Tiejun, Xu, Ruian
Biochemical and biophysical research communications 2019 v.512 no.3 pp. 598-603
Primate T-lymphotropic virus 1, T-lymphocytes, adults, cell lines, cell proliferation, half life, leukemia, neoplasm cells
Human T-cell leukemia virus 1 (HTLV-1), an oncogenic retrovirus, and Notch1 signaling, implicated in tumor formation and progression, are both associated with the development of adult T-cell leukemia (ATL). Here we explored the possibility of a mechanistic link between the two. We observed that the expression of Notch intracellular domain (NICD) was elevated in HTLV-1 infected cell lines. Knocking down of Notch1 in ATL cells repressed cellular proliferation and tumor formation both in vitro and in vivo. As a mechanism for these actions, we found that Tax activated Notch1 signaling by prolonging the half-life of NICD. We then showed that Tax, NICD, and RBP-jκ formed a ternary complex, that Tax enhanced the association of NICD with RBP-jκ, and that Tax, NICD, and RBP-jκ were bound to RBP-jκ-responsive elements. Hence, our results suggest that HTLV-1 promotes cellular proliferation and tumor formation of ATL cells by modulating Notch signaling via a posttranslational mechanism that involves interactions between Tax, NICD, and RBP-jκ.