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The Conserved Amino-terminal Domain of HSRP1 Alpha is Essential for Nuclear Protein Import

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Journal EMBO J
Date 1996 Apr 15
PMID 8617227
Citations 102
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Abstract

Nuclear proteins are targeted through the nuclear pore complex (NPC) in an energy-dependent reaction. The import reaction is mediated by nuclear localization sequences (NLS) in the substrate which are recognized by heterodimeric cytoplasmic receptors. hSRP1 alpha is an NLS-binding subunit of the human NLS receptor complex and is complexed in vivo with a second subunit of 97 kDa (p97). We show here that a short amino-terminal domain in hSRP1 alpha is necessary and sufficient for its interaction with p97. This domain is conserved in other SRP1-like proteins and its fusion to a cytoplasmic reporter protein is sufficient to promote complete nuclear import, circumventing the usual requirement for an NLS receptor interaction. The same amino-terminal domain inhibits import of NLS-containing proteins when added to an in vitro nuclear transport assay. While full-length hSRP alpha is able to leave the nucleus, the amino-terminal domain alone is not sufficient to promote exit. We conclude that hSRP1 alpha functions as an adaptor to tether NLS-containing substrates to the protein import machinery.

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References
1.
Newmeyer D, Forbes D . Nuclear import can be separated into distinct steps in vitro: nuclear pore binding and translocation. Cell. 1988; 52(5):641-53. DOI: 10.1016/0092-8674(88)90402-3. View

2.
Gorlich D, Henklein P, Laskey R, Hartmann E . A 41 amino acid motif in importin-alpha confers binding to importin-beta and hence transit into the nucleus. EMBO J. 1996; 15(8):1810-7. PMC: 450097. View

3.
Adam S, Marr R, Gerace L . Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors. J Cell Biol. 1990; 111(3):807-16. PMC: 2116268. DOI: 10.1083/jcb.111.3.807. View

4.
Adam S, Gerace L . Cytosolic proteins that specifically bind nuclear location signals are receptors for nuclear import. Cell. 1991; 66(5):837-47. DOI: 10.1016/0092-8674(91)90431-w. View

5.
Yano R, Oakes M, Yamaghishi M, Dodd J, Nomura M . Cloning and characterization of SRP1, a suppressor of temperature-sensitive RNA polymerase I mutations, in Saccharomyces cerevisiae. Mol Cell Biol. 1992; 12(12):5640-51. PMC: 360503. DOI: 10.1128/mcb.12.12.5640-5651.1992. View