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Identification of a functional bipartite nuclear localization signal in the tumor suppressor parafibromin

Oncogene volume 24, pages 6241–6248 (2005)Cite this article

A Corrigendum to this article was published on 01 February 2007

Abstract

Parafibromin is a putative tumor suppressor encoded by HRPT2, mutations in which have been implicated in the familial tumor syndrome hyperparathyroidism jaw tumor syndrome (HPT-JT), and sporadic parathyroid carcinoma. Recently, parafibromin has been shown to be an accessory factor for RNA polymerase II as part of the human Paf1 complex, suggesting, as has been shown for its yeast homologue (Cdc73), that it may have a role as an important regulator of transcription. Parafibromin has also been shown to interact with a histone methyltransferase complex that methylates histone H3 and to inhibit proliferation when overexpressed in mammalian cell lines. Despite these findings, the cellular localization of parafibromin has been controversial, with reports of both nuclear and nucleocytoplasmic localization. We have expressed wild-type and mutant parafibromin tagged with enhanced green fluorescent protein and have identified a functional bipartite nuclear localization signal (NLS) at residues 125–139 (nucleotides 373–417), KRAADEVLAEAKKPR, that is evolutionarily conserved and critical for the nuclear localization of parafibromin. We have also shown that the C-terminal arm of this bipartite NLS plays the primary role in nuclear localization. In support of these findings, specific HRPT2 mutations identified in HPT-JT or sporadic parathyroid carcinoma predicted to truncate parafibromin upstream of or within this NLS disrupt nuclear localization.

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Acknowledgements

Dr L Zhang, Flinders University, Adelaide, South Australia is thanked for his kind gift of EGFP vectors pEGF-C1 and pEGF-N1. This work was supported by the Australian National Health and Medical Research Council [302161]. DJM is the recipient of a Cancer Institute NSW Fellowship.

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  1. Department of Molecular Medicine, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, NSW 2065, Australia

    Michael A Hahn & Deborah J Marsh

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  1. Michael A Hahn
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  2. Deborah J Marsh
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Correspondence to Deborah J Marsh.

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Hahn, M., Marsh, D. Identification of a functional bipartite nuclear localization signal in the tumor suppressor parafibromin. Oncogene 24, 6241–6248 (2005). https://doi.org/10.1038/sj.onc.1208778

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