Nucleolar localization of cirhin, the protein mutated in North American Indian childhood cirrhosis

Journal Article · Sat Dec 10 00:00:00 EST 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.08.012· OSTI ID:20775320

Yu, Bin ^[1]; Mitchell, Grant A ^[1]; Richter, Andrea ^[1]

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1. Service de Genetique medicale, Centre de recherche, Hopital Sainte-Justine, Universite de Montreal, 3175 Cote Sainte-Catherine, Quebec, H3T1C5 (Canada)

Cirhin (NP{sub 1}16219), the product of the CIRH1A gene is mutated in North American Indian childhood cirrhosis (NAIC/CIRH1A, OMIM 604901), a severe autosomal recessive intrahepatic cholestasis. It is a 686-amino-acid WD40-repeat containing protein of unknown function that is predicted to contain multiple targeting signals, including an N-terminal mitochondrial targeting signal, a C-terminal monopartite nuclear localization signal (NLS) and a bipartite nuclear localization signal (BNLS). We performed the direct determination of subcellular localization of cirhin as a crucial first step in unraveling its biological function. Using EGFP and His-tagged cirhin fusion proteins expressed in HeLa and HepG2, cells we show that cirhin is a nucleolar protein and that the R565W mutation, for which all NAIC patients are homozygous, has no effect on subcellular localization. Cirhin has an active C-terminal monopartite nuclear localization signal (NLS) and a unique nucleolar localization signal (NrLS) between residues 315 and 432. The nucleolus is not known to be important specifically for intrahepatic cholestasis. These observations provide a new dimension in the study of hereditary cholestasis.

• OSTI ID: 20775320
• Journal Information: Experimental Cell Research, Vol. 311, Issue 2; Other Information: DOI: 10.1016/j.yexcr.2005.08.012; PII: S0014-4827(05)00389-7; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMERICAN INDIANS
AMINO ACIDS
BIOLOGICAL FUNCTIONS
GENES
MUTAGENESIS
MUTATIONS
PATIENTS
PROTEINS