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Title: The Hsp40 family chaperone protein DnaJB6 enhances Schlafen1 nuclear localization which is critical for promotion of cell-cycle arrest in T-cells
Author: Zhang, Yafeng ; Yang, Zhengmin ; Cao, Yonghao ; Zhang, Shijian ; Li, Hai ; Huang, Ying ; Ding, Yu-qiang ; Liu, Xiaolong
Source: BIOCHEMICAL JOURNAL
Issued Date: 2008
Volume: 413, Pages:239-250
Keyword: cyclin D1 ; DnaJB6 ; heat-shock protein ; nuclear ; import ; Schlafen1 (Slfn1) ; T-cell ; HEAT-SHOCK-PROTEIN ; PROTECTIVE EFFICACY ; LETHAL INFECTION ; QUIESCENCE ; MRJ ; MECHANISM ; SURVIVAL ; GENE ; D1 ; DIFFERENTIATION
Subject: Biochemistry & Molecular Biology
Corresponding Author: Liu, XL (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yueyang Rd, Shanghai 200031, Peoples R China,liux@sjbs.ac.cn
English Abstract: Tight control of cell-cycle progression is critical for T-lymphocytes to function properly. Slfn1 (Schlafen1) has been reported to play an important role in the establishment and maintenance of quiescence in T-lymphocytes. However, how Slfn1 accomplishes this critical function remains poorly understood. In the present study, we show that nuclear localization is a prerequisite for Slfn1 to induce cell-cycle arrest, with DnaJB6, identified as a new Slfn1-binding protein, playing a pivotal role in this process. DnaJB6, a chaperone protein of the DnaJ/Hsp (heat-shock protein) 40 family, stabilizes Slfn1 together with its partner Hsp70, and, more importantly, it enhances the nuclear import of Slfn1. Overexpression of DnaJB6 was found to increase Slfn1 nuclear accumulation and resulted in cell-cycle arrest, whereas, in DnaJB6 knock-down cells, Slfn1 was mainly sequestered in the cytoplasm and no cell-cycle arrest was observed. Furthermore, transgenic expression of DnaJB6 in T-lineage cells inhibited Slfn1's degradation, promoted its nuclear import and ultimately led to suppression of T-cell proliferation upon TCR (T-cell receptor) activation. In addition, DnaJB6 increased Slfn1's effect on its downstream target cyclin D1 in co-transfected cells. Altogether, our results demonstrate that DnaJB6 is necessary for translocation of Slfn1 into the nucleus, where Slfn1 down-regulates cyclin D1, induces cell-cycle arrest and programmes a quiescent state of T-cells.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1713
Appears in Collections:神经所(总)_期刊论文

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Zhang, Yafeng; Yang, Zhengmin; Cao, Yonghao; Zhang, Shijian; Li, Hai; Huang, Ying; Ding, Yu-qiang; Liu, Xiaolong.The Hsp40 family chaperone protein DnaJB6 enhances Schlafen1 nuclear localization which is critical for promotion of cell-cycle arrest in T-cells,BIOCHEMICAL JOURNAL,2008,413():239-250
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