Prolyl 4-hydroxylase 2 promotes B-cell lymphoma progression via hydroxylation of Carabin.

Jiang, Wei; Zhou, Xiaoyan; Li, Zengxia; Liu, Kaiyu; Wang, Weige; Tan, Renke; Cong, Xiaoji; Shan, Jiaoyu; Zhan, Yanxia; Cui, Zhaomeng; Jiang, Lizhi; Li, Quanfu; Shen, Suqin; Bai, Meirong; Cheng, Yunfeng; Li, Bin; Tan, Minjia; Ma, Dengke K; Liu, Jun O; Dang, Yongjun

Jiang, Wei; Zhou, Xiaoyan; Li, Zengxia; Liu, Kaiyu; Wang, Weige; Tan, Renke; Cong, Xiaoji; Shan, Jiaoyu; Zhan, Yanxia; Cui, Zhaomeng; Jiang, Lizhi; Li, Quanfu; Shen, Suqin; Bai, Meirong; Cheng, Yunfeng; Li, Bin; Tan, Minjia; Ma, Dengke K; Liu, Jun O; Dang, Yongjun.

Afiliación

Jiang W; Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
Zhou X; Cardiovascular Research Institute and.
Li Z; Department of Physiology, University of California San Francisco, San Francisco, CA.
Liu K; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Wang W; Department of Oncology, Shanghai Medical College, and.
Tan R; Institute of Pathology, Fudan University, Shanghai, China.
Cong X; Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
Shan J; Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
Zhan Y; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Cui Z; Department of Oncology, Shanghai Medical College, and.
Jiang L; Institute of Pathology, Fudan University, Shanghai, China.
Li Q; Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
Shen S; Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Bai M; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Cheng Y; Department of Hematology.
Li B; Biomedical Research Center, Zhongshan Hospital, and.
Tan M; Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
Ma DK; Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
Liu JO; Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
Dang Y; School of Life Science, Fudan University, Shanghai, China; and.

Blood ; 131(12): 1325-1336, 2018 03 22.

Article en En | MEDLINE | ID: mdl-29437589

RESUMEN

B-cell lymphomas are heterogeneous blood disorders with limited therapeutic options, largely because of their propensity to relapse and become refractory to treatments. Carabin, a key suppressor of B-cell receptor signaling and proliferation, is inactivated in B-cell lymphoma by unknown mechanisms. Here, we identify prolyl 4-hydroxylase 2 (P4HA2) as a specific proline hydroxylase of Carabin. Carabin hydroxylation leads to its proteasomal degradation, thereby activating the Ras/extracellular signal-regulated kinase pathway and increasing B-cell lymphoma proliferation. P4HA2 is undetectable in normal B cells but upregulated in the diffuse large B-cell lymphoma (DLBCL), driving Carabin inactivation and lymphoma proliferation. Our results indicate that P4HA2 is a potential prognosis marker for DLBCL and a promising pharmacological target for developing treatment of molecularly stratified B-cell lymphomas.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/metabolismo; Biomarcadores de Tumor/metabolismo; Proliferación Celular; Linfoma de Células B Grandes Difuso/metabolismo; Sistema de Señalización de MAP Quinasas; Proteínas de Neoplasias/metabolismo; Prolil Hidroxilasas/metabolismo; Proteínas Adaptadoras Transductoras de Señales/genética; Biomarcadores de Tumor/genética; Línea Celular Tumoral; Proteínas Activadoras de GTPasa; Humanos; Hidroxilación; Linfoma de Células B Grandes Difuso/genética; Linfoma de Células B Grandes Difuso/patología; Proteínas de Neoplasias/genética; Prolil Hidroxilasas/genética; Complejo de la Endopetidasa Proteasomal/genética; Complejo de la Endopetidasa Proteasomal/metabolismo; Proteolisis

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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Linfoma de Células B Grandes Difuso / Sistema de Señalización de MAP Quinasas / Proteínas Adaptadoras Transductoras de Señales / Proliferación Celular / Prolil Hidroxilasas / Proteínas de Neoplasias Límite: Humans Idioma: En Año: 2018 Tipo del documento: Article

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