2. Academic Validation
  3. FBXO22 targets ubiquitination and degradation of c-Cbl in leukemia

FBXO22 targets ubiquitination and degradation of c-Cbl in leukemia

  • Sci Rep. 2026 Feb 26;16(1):11190. doi: 10.1038/s41598-026-41123-z.
Juan Li # 1 2,  Li Ma # 1 3,  Jing Wang 1,  Wangwang Xu 1,  Yang Cheng 1,  Jialin Zhang 1 4,  Hairuo Cao 5,  Yu Wang 6,  Zhiwei Wang 7,  Hui Xu 8,  Yuyun Li 9,  Yingjie Zhang 10
Affiliations

Affiliations

  • 1 Bengbu Medical University Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, China.
  • 2 Department of Laboratory, Zaozhuang Municipal Hospital, Zaozhuang, 277102, Shandong, P.R. China.
  • 3 Department of Laboratory, Fuyang People's Hospital, Fuyang, 236000, Anhui, China.
  • 4 Department of Laboratory, The Second Hospital of Jiaxing, Jiaxing, Zhejiang, China.
  • 5 Anhui Province Key Laboratory of Immunology in Chronic Diseases, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, China.
  • 6 Department of Laboratory, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233030, Anhui, China.
  • 7 Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, China.
  • 8 Department of Clinical Laboratory Diagnostics, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, China.
  • 9 Bengbu Medical University Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, China. [email protected].
  • 10 Department of Clinical Laboratory Diagnostics, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, China. [email protected].
  • # Contributed equally.
PMID: 41748789 DOI: 10.1038/s41598-026-41123-z
Abstract

Leukemia is a malignant clonal disease originating from hematopoietic stem cells. Uncontrolled proliferation, impaired differentiation and maturation, accompanied by reduced Apoptosis is the most significant feature of leukemia. It has been suggested that c-Cbl is involved in the development of myeloid leukemia, but the upstream signal regulating its activity remains unclear. FBXO22 is an E3 ubiquitin Ligase belonging to the F-box protein family. We constructed stable cell lines of the overexpression of FBXO22 and c-Cbl, the knockdout of c-Cbl as well as FBXO22 + c-Cbl co-transfection. We used CCK-8 and FACS to measure the cell viability, cell cycle and cell differentiation, respectively. After overexpression of FBXO22, the proliferation of U937 and K562 cells was slowed down, the pro-apoptotic proteins were increased, the anti-apoptotic proteins were decreased, and the cells differentiated into the next stage. The result of c-Cbl knockdown was consistent with that of FBXO22 overexpression. Overexpression of c-Cbl showed the opposite result. In vivo experiments also showed that both FBXO22 overexpression and c-Cbl knockdown could inhibit the occurrence and development of leukemia. Immunoprecipitation result showed that FBXO22 interacted with c-Cbl and promoted ubiquitination and degradation of c-Cbl. Moreover, the results of rescue experiments showed that c-Cbl reversed the function of FBXO22 on leukemia cells. We identified that FBXO22 interacts with c-Cbl and promotes its ubiquitination and degradation to act as a tumor suppressor gene in leukemia. Our studies suggested that FBXO22 plays an Anticancer role by mediating ubiquitination and degradation of c-Cbl in leukemia.

Keywords

Degradation; FBXO22; Leukemia; Ubiquitination; c-Cbl.

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