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HTLV‐1 viral oncoprotein HBZ contributes to the enhancement of HAX‐1 stability by impairing the ubiquitination pathway
Author(s) -
Tanaka Yuka,
Mukai Risa,
Ohshima Takayuki
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30044
Subject(s) - ubiquitin , ubiquitin ligase , microbiology and biotechnology , retrovirus , human t lymphotropic virus 1 , cytoplasm , leukemia , biology , suppressor , downregulation and upregulation , hek 293 cells , cell culture , virology , virus , t cell leukemia , immunology , genetics , gene
Human T‐cell leukemia virus type 1 (HTLV‐1) is an oncogenic retrovirus that causes adult T‐cell leukemia (ATL). The viral protein HTLV‐1 basic leucine‐zipper factor (HBZ), which is constitutively expressed in all ATL patient cells, contributes toward the development of ATL; however, the underlying mechanism has not been elucidated yet. Here, we identified HS‐1‐associated protein X‐1 (HAX‐1) as a novel binding partner of HBZ. Interestingly, HAX‐1 specifically associated with HBZ‐US, but not HBZ‐SI, in the cytoplasm. HBZ suppressed the polyubiquitination levels of HAX‐1 protein by inhibiting the association HAX‐1 with F‐box protein 25 (FBXO25), which is a member of the SCF E3 ubiquitin ligase complex, and promoted the stabilization of HAX‐1 levels. In fact, the protein levels of HAX‐1 were significantly increased in HTLV‐1 infected and the overexpressing HBZ in uninfected T‐cell lines. Enhanced HAX‐1 correlated well to suppression of caspase 9 processing, suggesting that HBZ may contribute to the enhancement of antiapoptotic function for HAX‐1. Our results revealed a role for HBZ on HAX‐1 stabilization by abrogating the ubiquitination‐mediated degradation pathway, which may play an important role in understanding the potential mechanisms of HTLV‐1 related pathogenesis.