Nucleolar localization of parafibromin is mediated by three nucleolar localization signals.
Parafibromin is a putative tumor suppressor encoded by HRPT2 and implicated in parathyroid tumorigenesis. We previously reported a functional bipartite nuclear localization signal (NLS) at residues 125-139. We now demonstrate that parafibromin exhibits nucleolar localization, mediated by three nucleolar localization signals (NoLS) at resides 76-92, 192-194 and 393-409. These NoLS represent clusters of basic amino acids arginine and lysine, similar to those found in other nucleolar proteins, as well as being characteristic of NLSs. While parafibromin's bipartite NLS is the primary determinant of nuclear localization, it does not mediate nucleolar localization. In contrast, the three identified NoLSs play only a minor role in nuclear localization, but are critical for the nucleolar localization of parafibromin.
Hahn
Michael A
MA
Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, NSW 2065, Australia.
Marsh
Deborah J
DJ
D000595:Amino Acid Sequence; D002460:Cell Line; D002466:Cell Nucleolus / Q000737:chemistry / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D019913:Nuclear Localization Signals; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
C454900:CDC73 protein, human; D019913:Nuclear Localization Signals; D025521:Tumor Suppressor Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins