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SOX11 is a novel bi...
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Abdelrazak Morsy, Mohammad HamdyKarolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Alexandria Univ, Med Res Inst, Dept Appl Med Chem, Alexandria, Egypt.;Karolinska Inst, Lab Med, Alfred Nobels Alle 8B, S-14152 Stockholm, Sweden.
(author)
SOX11 is a novel binding partner and endogenous inhibitor of SAMHD1 ara-CTPase activity in mantle cell lymphoma
- Article/chapterEnglish2024
Publisher, publication year, extent ...
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American Society of Hematology,2024
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-532548
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-532548URI
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https://doi.org/10.1182/blood.2023022241DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:238237141URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:238774451URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Sterile alpha motif and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara -C) resistance in several hematological malignancies. Targeting SAMHD1's ara-CTPase activity has recently been demonstrated to enhance ara -C ef fi cacy in acute myeloid leukemia. Here, we identify the transcription factor SRY-related HMGbox containing protein 11 (SOX11) as a novel direct binding partner and fi rst known endogenous inhibitor of SAMHD1. SOX11 is aberrantly expressed not only in mantle cell lymphoma (MCL), but also in some Burkitt lymphomas. Coimmunoprecipitation of SOX11 followed by mass spectrometry in MCL cell lines identi fi ed SAMHD1 as the top SOX11 interaction partner, which was validated by proximity ligation assay. In vitro, SAMHD1 bound to the HMG box of SOX11 with low-micromolar af fi nity. In situ crosslinking studies further indicated that SOX11-SAMHD1 binding resulted in a reduced tetramerization of SAMHD1. Functionally, expression of SOX11 inhibited SAMHD1 ara-CTPase activity in a dose-dependent manner resulting in ara -C sensitization in cell lines and in a SOX11-inducible mouse model of MCL. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identi fi ed SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its fi rst known endogenous inhibitor with potentially important implications for clinical therapy strati fi cation.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Lilienthal, IngridKarolinska Institutet,Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Solna, Sweden.
(author)
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Lord, MartinUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)marlo206
(author)
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Merrien, MagaliKarolinska Institutet,Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
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Wasik, Agata MagdalenaKarolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
(author)
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Sureda-Gómez, MartaInst Invest Biomed August Pi Sunyer, Barcelona, Spain.
(author)
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Amador, VirginiaInst Invest Biomed August Pi Sunyer, Barcelona, Spain.;Ctr Invest Biomed Red Canc, Madrid, Spain.
(author)
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Johansson, Henrik J.Karolinska Institutet,Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
(author)
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Lehtiö, JanneKarolinska Institutet,Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
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Garcia-Torre, BeatrizInst Invest Biomed August Pi Sunyer, Barcelona, Spain.
(author)
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Martin-Subero, Jose IgnacioInst Invest Biomed August Pi Sunyer, Barcelona, Spain.;Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain.
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Tsesmetzis, NikolaosKarolinska Institutet,Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Solna, Sweden.
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Tao, SijiaEmory Univ, Ctr Viro Sci & Cure, Sch Med, Dept Pediat, Atlanta, GA USA.
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Schinazi, Raymond F.Emory Univ, Ctr Viro Sci & Cure, Sch Med, Dept Pediat, Atlanta, GA USA.
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Kim, BaekEmory Univ, Ctr Viro Sci & Cure, Sch Med, Dept Pediat, Atlanta, GA USA.
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Sorteberg, Agnes L.Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Solna, Sweden.
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Wickström, MalinKarolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Solna, Sweden.
(author)
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Sheppard, DevonFrancis Crick Inst, Macromol Struct Lab, London, England.
(author)
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Rassidakis, Georgios Z.Karolinska Institutet,Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX USA.
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Taylor, Ian A.Francis Crick Inst, Macromol Struct Lab, London, England.
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Christensson, BirgerKarolinska Institutet,Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
(author)
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Campo, EliasInst Invest Biomed August Pi Sunyer, Barcelona, Spain.;Ctr Invest Biomed Red Canc, Madrid, Spain.;Univ Barcelona, Hosp Clin Barcelona, Dept Anat Pathol, Hematopathol Sect, Barcelona, Spain.
(author)
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Herold, NikolasKarolinska Institutet,Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Solna, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Paediat Oncol, Stockholm, Sweden.
(author)
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Sander, BirgittaKarolinska Institutet,Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
(author)
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Karolinska InstitutetKarolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Alexandria Univ, Med Res Inst, Dept Appl Med Chem, Alexandria, Egypt.;Karolinska Inst, Lab Med, Alfred Nobels Alle 8B, S-14152 Stockholm, Sweden.
(creator_code:org_t)
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In:Blood: American Society of Hematology143:19, s. 1953-19640006-49711528-0020
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Lilienthal, Ingr ...
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Lord, Martin
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Merrien, Magali
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Wasik, Agata Mag ...
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Sureda-Gómez, Ma ...
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Amador, Virginia
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Tao, Sijia
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Kim, Baek
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Sorteberg, Agnes ...
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Wickström, Malin
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Sheppard, Devon
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Rassidakis, Geor ...
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Taylor, Ian A.
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Campo, Elias
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Herold, Nikolas
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