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KCTD5 regulates Ikaros degradation induced by chemotherapeutic drug etoposide in hematological cells.
Ma, Lan; Yin, Changqing; Zhang, Yi; Li, Jie; Shi, Liuzhi; Zhou, Tong; Huang, Xixi; Liu, Yaqi; Cao, Jiawei; Wu, Guang; Gu, Haihua; He, Licai.
Afiliação
  • Ma L; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medical and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
  • Yin C; Department of Nephropathy, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310007, China.
  • Zhang Y; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medical and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
  • Li J; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medical and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
  • Shi L; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medical and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
  • Zhou T; Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • Huang X; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medical and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
  • Liu Y; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medical and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
  • Cao J; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medical and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
  • Wu G; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medical and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
  • Gu H; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medical and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
  • He L; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, School of Laboratory Medical and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
Biol Chem ; 405(5): 341-349, 2024 May 27.
Article em En | MEDLINE | ID: mdl-38424700
ABSTRACT
Therapy-related leukemia carries a poor prognosis, and leukemia after chemotherapy is a growing risk in clinic, whose mechanism is still not well understood. Ikaros transcription factor is an important regulator in hematopoietic cells development and differentiation. In the absence of Ikaros, lymphoid cell differentiation is blocked at an extremely early stage, and myeloid cell differentiation is also significantly affected. In this work, we showed that chemotherapeutic drug etoposide reduced the protein levels of several isoforms of Ikaros including IK1, IK2 and IK4, but not IK6 or IK7, by accelerating protein degradation, in leukemic cells. To investigate the molecular mechanism of Ikaros degradation induced by etoposide, immunoprecipitation coupled with LC-MS/MS analysis was conducted to identify changes in protein interaction with Ikaros before and after etoposide treatment, which uncovered KCTD5 protein. Our further study demonstrates that KCTD5 is the key stabilizing factor of Ikaros and chemotherapeutic drug etoposide induces Ikaros protein degradation through decreasing the interaction of Ikaros with KCTD5. These results suggest that etoposide may induce leukemic transformation by downregulating Ikaros via KCTD5, and our work may provide insights to attenuate the negative impact of chemotherapy on hematopoiesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Transcrição Ikaros / Etoposídeo Limite: Humans Idioma: En Revista: Biol Chem Assunto da revista: BIOQUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Transcrição Ikaros / Etoposídeo Limite: Humans Idioma: En Revista: Biol Chem Assunto da revista: BIOQUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Alemanha