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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1325-1336
Number of pages12
JournalBlood
Volume131
Issue number12
DOIs
StatePublished - Mar 22 2018

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Prolyl 4-hydroxylase 2 promotes B-cell lymphoma progression via hydroxylation of Carabin'. Together they form a unique fingerprint.

Cite this