A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17
Abstract Recent data highlight the presence, in HIV-1-seropositive patients with lymphoma, of p17 variants (vp17s) endowed with B-cell clonogenicity, suggesting a role of vp17s in lymphomagenesis. We investigated the mechanisms responsible for the functional disparity on B cells between a wild-type...
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Nature Portfolio
2017
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oai:doaj.org-article:37164eca0acc4c81856e41043502f4a42021-12-02T15:05:53ZA single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p1710.1038/s41598-017-06848-y2045-2322https://doaj.org/article/37164eca0acc4c81856e41043502f4a42017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06848-yhttps://doaj.org/toc/2045-2322Abstract Recent data highlight the presence, in HIV-1-seropositive patients with lymphoma, of p17 variants (vp17s) endowed with B-cell clonogenicity, suggesting a role of vp17s in lymphomagenesis. We investigated the mechanisms responsible for the functional disparity on B cells between a wild-type p17 (refp17) and a vp17 named S75X. Here, we show that a single Arginine (R) to Glycine (G) mutation at position 76 in the refp17 backbone (p17R76G), as in the S75X variant, is per se sufficient to confer a B-cell clonogenic potential to the viral protein and modulate, through activation of the PTEN/PI3K/Akt signaling pathway, different molecules involved in apoptosis inhibition (CASP-9, CASP-7, DFF-45, NPM, YWHAZ, Src, PAX2, MAPK8), cell cycle promotion and cancer progression (CDK1, CDK2, CDK8, CHEK1, CHEK2, GSK-3 beta, NPM, PAK1, PP2C-alpha). Moreover, the only R to G mutation at position 76 was found to strongly impact on protein folding and oligomerization by altering the hydrogen bond network. This generates a conformational shift in the p17 R76G mutant which enables a functional epitope(s), masked in refp17, to elicit B-cell growth-promoting signals after its interaction with a still unknown receptor(s). Our findings offer new opportunities to understand the molecular mechanisms accounting for the B-cell growth-promoting activity of vp17s.Cinzia GiagulliPasqualina D’UrsiWangxiao HeSimone ZorzanFrancesca CaccuriKristen VarneyAlessandro OrroStefania MarsicoBenoît OtjacquesCarlo LaudannaLuciano MilanesiRiccardo DolcettiSimona FiorentiniWuyuan LuArnaldo CarusoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
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Medicine R Science Q Cinzia Giagulli Pasqualina D’Ursi Wangxiao He Simone Zorzan Francesca Caccuri Kristen Varney Alessandro Orro Stefania Marsico Benoît Otjacques Carlo Laudanna Luciano Milanesi Riccardo Dolcetti Simona Fiorentini Wuyuan Lu Arnaldo Caruso A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17 |
| description |
Abstract Recent data highlight the presence, in HIV-1-seropositive patients with lymphoma, of p17 variants (vp17s) endowed with B-cell clonogenicity, suggesting a role of vp17s in lymphomagenesis. We investigated the mechanisms responsible for the functional disparity on B cells between a wild-type p17 (refp17) and a vp17 named S75X. Here, we show that a single Arginine (R) to Glycine (G) mutation at position 76 in the refp17 backbone (p17R76G), as in the S75X variant, is per se sufficient to confer a B-cell clonogenic potential to the viral protein and modulate, through activation of the PTEN/PI3K/Akt signaling pathway, different molecules involved in apoptosis inhibition (CASP-9, CASP-7, DFF-45, NPM, YWHAZ, Src, PAX2, MAPK8), cell cycle promotion and cancer progression (CDK1, CDK2, CDK8, CHEK1, CHEK2, GSK-3 beta, NPM, PAK1, PP2C-alpha). Moreover, the only R to G mutation at position 76 was found to strongly impact on protein folding and oligomerization by altering the hydrogen bond network. This generates a conformational shift in the p17 R76G mutant which enables a functional epitope(s), masked in refp17, to elicit B-cell growth-promoting signals after its interaction with a still unknown receptor(s). Our findings offer new opportunities to understand the molecular mechanisms accounting for the B-cell growth-promoting activity of vp17s. |
| format |
article |
| author |
Cinzia Giagulli Pasqualina D’Ursi Wangxiao He Simone Zorzan Francesca Caccuri Kristen Varney Alessandro Orro Stefania Marsico Benoît Otjacques Carlo Laudanna Luciano Milanesi Riccardo Dolcetti Simona Fiorentini Wuyuan Lu Arnaldo Caruso |
| author_facet |
Cinzia Giagulli Pasqualina D’Ursi Wangxiao He Simone Zorzan Francesca Caccuri Kristen Varney Alessandro Orro Stefania Marsico Benoît Otjacques Carlo Laudanna Luciano Milanesi Riccardo Dolcetti Simona Fiorentini Wuyuan Lu Arnaldo Caruso |
| author_sort |
Cinzia Giagulli |
| title |
A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17 |
| title_short |
A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17 |
| title_full |
A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17 |
| title_fullStr |
A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17 |
| title_full_unstemmed |
A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17 |
| title_sort |
single amino acid substitution confers b-cell clonogenic activity to the hiv-1 matrix protein p17 |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/37164eca0acc4c81856e41043502f4a4 |
| work_keys_str_mv |
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