Identification and characterization of nuclear and nucleolar localization signals in 58-kDa microspherule protein (MSP58)

Journal of Biomedical Science

Ding-Yen Lin⁵  Wen-Chang Chang²  Yu-San Yang⁷  Yi-Huan Tsou³  Mei-Hsiang Wu⁴  Yi-Chao Lee¹  Chang-Han Chen⁶  Chi-Wu Chiang⁸  Chuan-Pin Yang⁴ 

[1] Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan, ROC;Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 11031, Taiwan, ROC;Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, ROC;Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 70101, Taiwan, ROC;Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan, ROC;Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan, ROC;Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, ROC;Infectious Diseases and Signaling Research Center, National Cheng Kung University, Tainan 70101, Taiwan, ROC

关键词: Importins;    Nucleolar localization signal;    Nuclear localization signal;    Nucleolus;    58-kDa Microspherule Protein;   

Others  :  1213950
DOI  :  10.1186/s12929-015-0136-0

 received in 2014-12-02, accepted in 2015-04-21,  发布年份 2015

【 摘 要 】

Background

MSP58 is a nucleolar protein associated with rRNA transcription and cell proliferation. Its mechanism of translocation into the nucleus or the nucleolus, however, is not entirely known. In order to address this lack, the present study aims to determine a crucial part of this mechanism: the nuclear localization signal (NLS) and the nucleolar localization signal (NoLS) associated with the MSP58 protein.

Results

We have identified and characterized two NLSs in MSP58. The first is located between residues 32 and 56 (NLS1) and constitutes three clusters of basic amino acids (KRASSQALGTIPKRRSSSRFIKRKK); the second is situated between residues 113 and 123 (NLS2) and harbors a monopartite signal (PGLTKRVKKSK). Both NLS1 and NLS2 are highly conserved among different vertebrate species. Notably, one bipartite motif within the NLS1 (residues 44–56) appears to be absolutely necessary for MSP58 nucleolar localization. By yeast two-hybrid, pull-down, and coimmunoprecipitation analysis, we show that MSP58 binds to importin α1 and α6, suggesting that nuclear targeting of MSP58 utilizes a receptor-mediated and energy-dependent import mechanism. Functionally, our data show that both nuclear and nucleolar localization of MSP58 are crucial for transcriptional regulation on p21 and ribosomal RNA genes, and context-dependent effects on cell proliferation.

Conclusions

Results suggest that MSP58 subnuclear localization is regulated by two nuclear import signals, and that proper subcellular localization of MSP58 is critical for its role in transcriptional regulation. Our study reveals a molecular mechanism that controls nuclear and nucleolar localization of MSP58, a finding that might help future researchers understand the MSP58 biological signaling pathway.

【 授权许可】

   
2015 Yang et al.; licensee BioMed Central.

【 图 表 】

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