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Molecular and Cellular Biology, January 2004, p. 487-501, Vol. 24, No. 2
0270-7306/04/$08.00+0 DOI: 10.1128/MCB.24.2.487-501.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Np73ß Is Active in Transactivation and Growth Suppression
Gang Liu, Susan Nozell, Hui Xiao, and Xinbin Chen*
Department of Cell Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294-0005
Received 29 May 2003/
Returned for modification 30 July 2003/
Accepted 23 October 2003
p73, a p53 family protein, shares significant sequence homolog and functional similarity with p53. However, unlike p53, p73 has at least seven alternatively spliced isoforms with different carboxyl termini (p73
-
). Moreover, the p73 gene can be transcribed from a cryptic promoter located in intron 3, producing seven more proteins (
Np73
-
).
Np73, which does not contain the N-terminal activation domain in p73, has been thought to be transcriptionally inactive and dominant negative over p53 or p73. To systemically analyze the activity of the
N variant, we generated stable cell lines, which inducibly express
Np73
,
Np73ß, and various
Np73ß mutants by using the tetracycline-inducible expression system. Surprisingly, we found that
Np73ß is indeed active in inducing cell cycle arrest and apoptosis. Importantly, we found that, when
Np73ß is expressed at a physiologically relevant level, it is capable of suppressing cell growth. We then demonstrated that these
Np73ß activities are not cell type specific. We showed that the 13 unique residues at the N terminus are required for
Np73ß to suppress cell growth. We also found that, among the 13 residues, residues 6 to 10 are critical to
Np73ß function. Furthermore, we found that
Np73ß is capable of inducing some p53 target genes, albeit to a lesser extent than does p73ß. Finally, we found that the 13 unique residues, together with the N-terminal PXXP motifs, constitute a novel activation domain. Like
Np73ß,
Np73
is active in transactivation. However, unlike
Np73ß,
Np73
is inactive in suppressing cell growth. Our data, together with others' previous findings, suggest that
Np73ß may have distinct functions under certain cellular circumstances.
* Corresponding author. Mailing address: MCLM 660, Department of Cell Biology, The University of Alabama at Birmingham, 1530 3rd Ave. S., Birmingham, AL 35294-0005. Phone: (205) 975-1798. Fax: (205) 934-0950. E-mail:
xchen{at}uab.edu.
Molecular and Cellular Biology, January 2004, p. 487-501, Vol. 24, No. 2
0022-538X/04/$08.00+0 DOI: 10.1128/MCB.24.2.487-501.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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