Constitutive DUSP2 expression enhances lymphoid cell proliferation by activating CDK1 and promotes lymphomagenesis

Yu Qian; Jutatip Panaampon; Bjoern Chapuy; Xueyan Zhang; Xiujuan Zhao; Zhe Wang; Pengfei Zhang; Tongchai Payungwong; Aretina Zhang; Qiang Ke; Jing Zhong; Ping Yuan; Lei Zhang; Min Hong; Il Kyu Choi; Jiankun Guan; Dinis Pedro Calado; Scott Rodig; Olga Pozdnyakova; Klaus Rajewsky; Susana A. Godinho; Siwanon Jirawatnotai; Hao Wu; Margaret A. Shipp; Stephanie K. Dougan; Baochun Zhang

doi:10.1016/j.celrep.2026.117652

Constitutive DUSP2 expression enhances lymphoid cell proliferation by activating CDK1 and promotes lymphomagenesis

Yu Qian
, Jutatip Panaampon
, Bjoern Chapuy
, Xueyan Zhang
, Xiujuan Zhao
, Zhe Wang
, Pengfei Zhang
, Tongchai Payungwong
, Aretina Zhang
, Qiang Ke
, Jing Zhong
, Ping Yuan
, Lei Zhang
, Min Hong
, Il Kyu Choi
, Jiankun Guan
, Dinis Pedro Calado
, Scott Rodig
, Olga Pozdnyakova
, Klaus Rajewsky

Susana A. Godinho, Siwanon Jirawatnotai, Hao Wu, Margaret A. Shipp, Stephanie K. Dougan, Baochun Zhang

Department of Pharmacology

Dana-Farber Cancer Institute
Harvard Medical School
Charité-Universitätsmedizin Berlin
The First Affiliated Hospital of Guangzhou Medical University
Tianjin Medical University
Children's Hospital
Siriraj Hospital
Hangzhou Normal University
First Affiliated Hospital of University of South China
The First Affiliated Hospital of Zhengzhou University
Shanxi Dayi Hospital
First Affiliated Hospital of Kunming Medical University
The Francis Crick Institute
King's College London
Brigham and Women's Hospital
Max Delbrueck Center for Molecular Medicine and Charité- Universiätsmedizin Berlin
Barts and The London School of Medicine and Dentistry

Research output: Contribution to journal › Article › peer-review

Abstract

DUSP2 is known as a nuclear dual-specificity phosphatase, highly restricted to immune cells. Its expression is induced by antigenic and mitogenic stimuli and has been implicated in immune cell differentiation and functions. However, its role in immune cell mitotic proliferation and hematologic malignancies has not been rigorously examined. Here, we show DUSP2 is highly expressed in human B-cell, T cell, and other hematologic malignancies. Ablating DUSP2 expression in lymphoma cell lines decreases growth and viability. In mice, transgenic Dusp2 expression promotes B-cell and T cell proliferation, and malignant transformation. Mechanistically, DUSP2 promotes cell cycle progression by activating CDK1 through dephosphorylation at inhibitory Tyr15 and Thr14, which is mediated not by its own phosphatase activity, but instead by a structural motif that recruits CDC25 phosphatases. This work reveals an unexpected oncogenic role for DUSP2 in lymphoid malignancies and the function of a structural motif, which represents an appealing target site for therapeutic intervention.

Original language	English
Article number	117652
Journal	Cell Reports
Volume	45
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2026.117652
Publication status	Published - 28 Jul 2026

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CDC25
CDK1
DUSP2, PAC-1
cell cycle
hematologic malignancies
immune cell
lymphomagenesis

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10.1016/j.celrep.2026.117652

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Qian, Y., Panaampon, J., Chapuy, B., Zhang, X., Zhao, X., Wang, Z., Zhang, P., Payungwong, T., Zhang, A., Ke, Q., Zhong, J., Yuan, P., Zhang, L., Hong, M., Choi, I. K., Guan, J., Calado, D. P., Rodig, S., Pozdnyakova, O., ... Zhang, B. (2026). Constitutive DUSP2 expression enhances lymphoid cell proliferation by activating CDK1 and promotes lymphomagenesis. Cell Reports, 45(7), Article 117652. https://doi.org/10.1016/j.celrep.2026.117652

@article{ec7843681928470787fe8e03ad4cd01b,

title = "Constitutive DUSP2 expression enhances lymphoid cell proliferation by activating CDK1 and promotes lymphomagenesis",

abstract = "DUSP2 is known as a nuclear dual-specificity phosphatase, highly restricted to immune cells. Its expression is induced by antigenic and mitogenic stimuli and has been implicated in immune cell differentiation and functions. However, its role in immune cell mitotic proliferation and hematologic malignancies has not been rigorously examined. Here, we show DUSP2 is highly expressed in human B-cell, T cell, and other hematologic malignancies. Ablating DUSP2 expression in lymphoma cell lines decreases growth and viability. In mice, transgenic Dusp2 expression promotes B-cell and T cell proliferation, and malignant transformation. Mechanistically, DUSP2 promotes cell cycle progression by activating CDK1 through dephosphorylation at inhibitory Tyr15 and Thr14, which is mediated not by its own phosphatase activity, but instead by a structural motif that recruits CDC25 phosphatases. This work reveals an unexpected oncogenic role for DUSP2 in lymphoid malignancies and the function of a structural motif, which represents an appealing target site for therapeutic intervention.",

keywords = "CDC25, CDK1, DUSP2, PAC-1, cell cycle, hematologic malignancies, immune cell, lymphomagenesis",

author = "Yu Qian and Jutatip Panaampon and Bjoern Chapuy and Xueyan Zhang and Xiujuan Zhao and Zhe Wang and Pengfei Zhang and Tongchai Payungwong and Aretina Zhang and Qiang Ke and Jing Zhong and Ping Yuan and Lei Zhang and Min Hong and Choi, \{Il Kyu\} and Jiankun Guan and Calado, \{Dinis Pedro\} and Scott Rodig and Olga Pozdnyakova and Klaus Rajewsky and Godinho, \{Susana A.\} and Siwanon Jirawatnotai and Hao Wu and Shipp, \{Margaret A.\} and Dougan, \{Stephanie K.\} and Baochun Zhang",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/",

year = "2026",

month = jul,

day = "28",

doi = "10.1016/j.celrep.2026.117652",

language = "English",

volume = "45",

journal = "Cell Reports",

issn = "2639-1856",

publisher = "Elsevier B.V.",

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Qian, Y, Panaampon, J, Chapuy, B, Zhang, X, Zhao, X, Wang, Z, Zhang, P, Payungwong, T, Zhang, A, Ke, Q, Zhong, J, Yuan, P, Zhang, L, Hong, M, Choi, IK, Guan, J, Calado, DP, Rodig, S, Pozdnyakova, O, Rajewsky, K, Godinho, SA, Jirawatnotai, S, Wu, H, Shipp, MA, Dougan, SK & Zhang, B 2026, 'Constitutive DUSP2 expression enhances lymphoid cell proliferation by activating CDK1 and promotes lymphomagenesis', Cell Reports, vol. 45, no. 7, 117652. https://doi.org/10.1016/j.celrep.2026.117652

TY - JOUR

T1 - Constitutive DUSP2 expression enhances lymphoid cell proliferation by activating CDK1 and promotes lymphomagenesis

AU - Qian, Yu

AU - Panaampon, Jutatip

AU - Chapuy, Bjoern

AU - Zhang, Xueyan

AU - Zhao, Xiujuan

AU - Wang, Zhe

AU - Zhang, Pengfei

AU - Payungwong, Tongchai

AU - Zhang, Aretina

AU - Ke, Qiang

AU - Zhong, Jing

AU - Yuan, Ping

AU - Zhang, Lei

AU - Hong, Min

AU - Choi, Il Kyu

AU - Guan, Jiankun

AU - Calado, Dinis Pedro

AU - Rodig, Scott

AU - Pozdnyakova, Olga

AU - Rajewsky, Klaus

AU - Godinho, Susana A.

AU - Jirawatnotai, Siwanon

AU - Wu, Hao

AU - Shipp, Margaret A.

AU - Dougan, Stephanie K.

AU - Zhang, Baochun

PY - 2026/7/28

Y1 - 2026/7/28

N2 - DUSP2 is known as a nuclear dual-specificity phosphatase, highly restricted to immune cells. Its expression is induced by antigenic and mitogenic stimuli and has been implicated in immune cell differentiation and functions. However, its role in immune cell mitotic proliferation and hematologic malignancies has not been rigorously examined. Here, we show DUSP2 is highly expressed in human B-cell, T cell, and other hematologic malignancies. Ablating DUSP2 expression in lymphoma cell lines decreases growth and viability. In mice, transgenic Dusp2 expression promotes B-cell and T cell proliferation, and malignant transformation. Mechanistically, DUSP2 promotes cell cycle progression by activating CDK1 through dephosphorylation at inhibitory Tyr15 and Thr14, which is mediated not by its own phosphatase activity, but instead by a structural motif that recruits CDC25 phosphatases. This work reveals an unexpected oncogenic role for DUSP2 in lymphoid malignancies and the function of a structural motif, which represents an appealing target site for therapeutic intervention.

AB - DUSP2 is known as a nuclear dual-specificity phosphatase, highly restricted to immune cells. Its expression is induced by antigenic and mitogenic stimuli and has been implicated in immune cell differentiation and functions. However, its role in immune cell mitotic proliferation and hematologic malignancies has not been rigorously examined. Here, we show DUSP2 is highly expressed in human B-cell, T cell, and other hematologic malignancies. Ablating DUSP2 expression in lymphoma cell lines decreases growth and viability. In mice, transgenic Dusp2 expression promotes B-cell and T cell proliferation, and malignant transformation. Mechanistically, DUSP2 promotes cell cycle progression by activating CDK1 through dephosphorylation at inhibitory Tyr15 and Thr14, which is mediated not by its own phosphatase activity, but instead by a structural motif that recruits CDC25 phosphatases. This work reveals an unexpected oncogenic role for DUSP2 in lymphoid malignancies and the function of a structural motif, which represents an appealing target site for therapeutic intervention.

KW - CDC25

KW - CDK1

KW - DUSP2, PAC-1

KW - cell cycle

KW - hematologic malignancies

KW - immune cell

KW - lymphomagenesis

UR - https://www.scopus.com/pages/publications/105044246318

U2 - 10.1016/j.celrep.2026.117652

DO - 10.1016/j.celrep.2026.117652

M3 - Article

AN - SCOPUS:105044246318

SN - 2639-1856

VL - 45

JO - Cell Reports

JF - Cell Reports

IS - 7

M1 - 117652

ER -

Constitutive DUSP2 expression enhances lymphoid cell proliferation by activating CDK1 and promotes lymphomagenesis

Abstract

UN SDGs

Keywords

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