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

Abstract

BackgroundMSP58 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.ResultsWe 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.ConclusionsResults 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-015-0136-0) contains supplementary material, which is available to authorized users.

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

“…Due to a publisher error in the original version of this article [ 1 ], ‘8A’ was superimposed on the 10A – EGFP image in Fig. 2C.…”

Mps1 regulates spindle morphology through MCRS1 to promote chromosome alignment

“…, 2016). During interphase, MCRS1 localizes to the nucleus and nucleolus to regulate gene expression, but it moves to the minus ends of kinetochore microtubules during mitosis to regulate their dynamics (Meunier and Vernos, 2011; Cavazza and Vernos, 2015; Yang et al. , 2015).…”