P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression
文献类型：期刊论文
| 作者 | Li, Quanfu11; Liu, Yiyang11; Wu, Jingxian10; Zhu, Zewen11; Fan, Jianjun9; Zhai, Linhui8; Wang, Ziruoyu11; Du, Guiping7; Zhang, Ling6; Hu, Junchi9 |
| 刊名 | LEUKEMIA
 |
| 出版日期 | 2024-06-22 |
| 页码 | 13 |
| ISSN号 | 0887-6924 |
| DOI | 10.1038/s41375-024-02313-8 |
| 通讯作者 | Dang, Yongjun(yjdang@cqmu.edu.cn) ; Jiang, Wei(jiangw@fudan.edu.cn) |
| 英文摘要 | Aberrations in the Hedgehog (Hh) signaling pathway are significantly prevailed in various cancers, including B-cell lymphoma. A critical facet of Hh signal transduction involves the dynamic regulation of the suppressor of fused homolog (SUFU)-glioma-associated oncogene homolog (GLI) complex within the kinesin family member 7 (KIF7)-supported ciliary tip compartment. However, the specific post-translational modifications of SUFU-GLI complex within this context have remained largely unexplored. Our study reveals a novel regulatory mechanism involving prolyl 4-hydroxylase 2 (P4HA2), which forms a complex with KIF7 and is essential for signal transduction of Hh pathway. We demonstrate that, upon Hh pathway activation, P4HA2 relocates alongside KIF7 to the ciliary tip. Here, it hydroxylates SUFU to inhibit its function, thus amplifying the Hh signaling. Moreover, the absence of P4HA2 significantly impedes B lymphoma progression. This effect can be attributed to the suppression of Hh signaling in stromal fibroblasts, resulting in decreased growth factors essential for malignant proliferation of B lymphoma cells. Our findings highlight the role of P4HA2-mediated hydroxylation in modulating Hh signaling and propose a novel stromal-targeted therapeutic strategy for B-cell lymphoma. |
| WOS关键词 | NEGATIVE REGULATOR ; GLI PROTEINS ; STABILITY ; PATHWAY ; SUPPRESSOR ; NOTCH ; PHD3 ; PKA ; WNT |
| 资助项目 | National Natural Science Foundation of China (National Science Foundation of China) |
| WOS研究方向 | Oncology ; Hematology |
| 语种 | 英语 |
| WOS记录号 | WOS:001251877800001 |
| 出版者 | SPRINGERNATURE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/311911]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Dang, Yongjun; Jiang, Wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou 310058, Peoples R China 3.Zhejiang Univ, Dept Cell Biol, Sch Med, Hangzhou 310058, Peoples R China 4.Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21287 USA 5.Univ Calif San Francisco, Cardiovasc Res Inst, Dept Physiol, San Francisco, CA 94158 USA 6.Chongqing Med Univ, Basic Med Res & Innovat Ctr Novel Target & Therape, Minist Educ, Affiliated Hosp 2, Chongqing 400016, Peoples R China 7.Zhejiang Univ, Womens Hosp, Sch Med, Hangzhou 310058, Peoples R China 8.Tongji Univ, Shanghai Peoples Hosp 4, Translat Res Inst Brain & Brain Like Intelligence, Sch Med, Shanghai 200434, Peoples R China 9.Chongqing Med Univ, Coll Pharm, Basic Med Res & Innovat Ctr Novel Target & Therape, Minist Educ, Chongqing 400016, Peoples R China 10.First Affiliated Hosp Chongqing Med Univ, Chongqing Med Univ, Coll Basic Med, Mol Med Diagnost & Testing Ctr,Dept Pathol,Affilia, Chongqing 400016, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Quanfu,Liu, Yiyang,Wu, Jingxian,et al. P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression[J]. LEUKEMIA,2024:13. |
| APA | Li, Quanfu.,Liu, Yiyang.,Wu, Jingxian.,Zhu, Zewen.,Fan, Jianjun.,...&Jiang, Wei.(2024).P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression.LEUKEMIA,13. |
| MLA | Li, Quanfu,et al."P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression".LEUKEMIA (2024):13. |
入库方式： OAI收割
来源：上海药物研究所
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