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Molecular and Cellular Biology, September 1999, p. 6306-6317, Vol. 19, No. 9
Human Retrovirus Pathogenesis
Section1 and Confocal
Microscopy,2 ABL-Basic Research Program,
National Cancer Institute-Frederick Cancer Research and Development
Center, Frederick, Maryland 21702-1201
Received 5 April 1999/Returned for modification 10 May
1999/Accepted 14 June 1999
The nuclear export of the unspliced type D retrovirus mRNA depends
on the cis-acting constitutive transport RNA element (CTE) that has been shown to interact with the human TAP (hTAP) protein promoting the export of the CTE-containing mRNAs. We report here that
hTAP is a 619-amino-acid protein extending the previously identified
protein by another 60 residues at the N terminus and that hTAP shares
high homology with the predicted rat and mouse TAP proteins. We found
that hTAP is a nuclear protein that accumulates in the nuclear rim and
the nucleoplasm. We further demonstrated that hTAP is able to shuttle
between the nucleus and the cytoplasm. Identification of the signals
responsible for nuclear import (NLS) and export (NES) revealed that
they are distinct but partially overlapping. NLS and NES of hTAP are
active transferable signals that do not share similarities with known
elements. The C-terminal portion contributes further to hTAP's nuclear
retention and contains a signal(s) for nuclear rim association. Taken
together, our data show that hTAP is a dynamic protein capable of
bidirectional trafficking across the nuclear envelope. These data
further support hTAP's role as an export factor of the CTE-containing mRNAs.
0270-7306/99/$04.00+0
Identification of Novel Import and Export Signals
of Human TAP, the Protein That Binds to the Constitutive Transport
Element of the Type D Retrovirus mRNAs
*
Corresponding author. Mailing address: ABL-Basic
Research Program, Bldg. 535, Rm. 110, NCI-FCRDC, Frederick, MD
21702-1201. Phone: (301) 846-5159. Fax: (301) 846-7146. E-mail:
felber{at}mail.ncifcrf.gov.
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