期刊
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
卷 83, 期 2, 页码 300-308出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/09168451.2018.1536516
关键词
Cell growth; cell-penetrating protein; protein therapy; SOCS2
类别
资金
- Japan Society for the Promotion of Science (JSPS) [21688008, 24580148]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan [S1491007]
- Grants-in-Aid for Scientific Research [24580148, 21688008] Funding Source: KAKEN
Suppressor of cytokine signaling (SOCS) 2, a negative regulator of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), which is associated with acromegaly and cancers, is a promising candidate molecule for treating various diseases. To facilitate its use in protein therapy, we designed and constructed a human SOCS2 protein containing a membrane-permeable peptide sequence and expressed it in an Escherichia coli system. The partially purified recombinant protein was effectively delivered into several cancer cell lines and inhibited cell growth. Biochemical analysis showed that the recombinant SOCS2 protein interacted with growth hormone receptor (GHR) and downregulated GH-STAT5 signaling target genes. Our results suggest that the designed cell-penetrating SOCS2 protein will be useful in intercellular protein therapy to cure cancers.Abbreviations: SOCS: suppressor of cytokine signaling; GH: growth hormone; GHR: growth hormone receptor; IGF-1: insulin-like growth factor 1; CP: cell-penetrating; STAT: signal transducer and activator of transcription; JAK: Janus kinase; HNF: hepatocyte nuclear factor; MTM: membrane-translocating motif; HIV: human immunodeficiency virus
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