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ZBTB24 regulates the apoptosis of human T cells via CDCA7/TRAIL-receptor axis.
Qin, Xiao-Yuan; Feng, Jing; Chen, Ge; Dou, Xun-Wu; Dai, Xiao-Qiu; Dong, Hong-Liang; Gong, Fang-Yuan; Xiao, Fei; Zhao, Ying; Gao, Xiao-Ming; Wang, Jun.
Afiliação
  • Qin XY; Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • Feng J; Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • Chen G; Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • Dou XW; Department of Otolaryngology, Children's Hospital of Soochow University, Suzhou, China.
  • Dai XQ; Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • Dong HL; Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • Gong FY; Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.
  • Xiao F; Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.
  • Zhao Y; Department of Pathophysiology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.
  • Gao XM; Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China. Electronic address: xmgao@suda.edu.cn.
  • Wang J; Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China. Electronic address: jwang79@suda.edu.cn.
Biochem Biophys Res Commun ; 514(1): 259-265, 2019 06 18.
Article em En | MEDLINE | ID: mdl-31030944
Mutations in ZBTB24 and CDCA7 cause the Immunodeficiency, Centromeric Instability and Facial Anomalies syndrome type 2 and 3 (ICF2/3), respectively. Most ICF2 patients carry ZBTB24 nonsense mutations and are thus ZBTB24-deficient. Although the immune deficiency in ICF2 patients is primarily regarded as a B-cell defect due to the greatly reduced serum antibodies and circulating memory B cells, the reduced expansions of PBMCs stimulated by mitogens or recall antigens suggest a T-cell defect in these patients as well. However, the molecular mechanisms behind this T-cell dysfunction remain unknown. In the present study, we demonstrated that ZBTB24-deficiency significantly represses the proliferation of human T cells by promoting TRAIL-induced cell death. Downregulation of ZBTB24 in both Jurkat and human primary T cells upregulates the expression of TRAIL and/or its death receptors (TRAIL-R1/2), and induces significant amount of cells to undergo apoptosis. The profound survival defects of ZBTB24-deficient cells are largely reversed by blocking TRAIL/TRAIL-R interactions with exogenous recombinant TRAIL-R2. Moreover, ZBTB24-downregulation reduces the expression of CDCA7, and knockdown of the latter in human T cells results in a phenotype resembling that caused by ZBTB24-depletion. Functionally, overexpression of CDCA7 abrogates the increased apoptosis in ZBTB24-depleted Jurkat T cells. Together, these data indicated that ZBTB24 regulates human T-cell apoptosis via CDCA7/TRAIL-R axis. Our study thus not only provides a molecular explanation for the T-cell defects in ZBTB24-deficient ICF2 patients, but also highlights a convergence between ZBTB24 and CDCA7, the two ICF genes, in modulating the functions of T cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Proteínas Nucleares / Linfócitos T / Ligante Indutor de Apoptose Relacionado a TNF Limite: Humans Idioma: En Revista: Biochem Biophys Res Commun Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Repressoras / Proteínas Nucleares / Linfócitos T / Ligante Indutor de Apoptose Relacionado a TNF Limite: Humans Idioma: En Revista: Biochem Biophys Res Commun Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos