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[Cancer Research 59, 5902-5907, December 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 5902-5907, December 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Deletion of the COOH-Terminal Region of p73{alpha} Enhances Both Its Transactivation Function and DNA-binding Activity but Inhibits Induction of Apoptosis in Mammalian Cells1

Toshinori Ozaki, Masahiko Naka, Naoyuki Takada, Mitsuhiro Tada, Shigeru Sakiyama and Akira Nakagawara2

Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260-8717 [T. O., M. N., N. T., S. S., A. N.], and Division of Cell Biology, Cancer Institute, Hokkaido University School of Medicine, Sapporo 060-8638 [M. T.], Japan

The candidate tumor suppressor p73 has a high sequence homology with p53 within the NH2-terminal transactivation domain, the sequence-specific DNA-binding region, and the oligomerization domain. However, p73{alpha}, which is most abundantly expressed in many tissues and cells among the alternatively spliced forms of p73, has an additional long COOH-terminal tail that might distinguish the function of p53 and p73{alpha} or other p73 splicing variants. To examine the functional role of the p73{alpha} COOH-terminal region, we generated a series of p73{alpha} truncation mutants including p73{alpha}(1–247) (retaining only a transactivation domain), p73{alpha}(1–427) (lacking the most COOH-terminal region including a SAM domain), and p73{alpha}(1–548) (deleting an extreme COOH-terminal region except a SAM domain). When transfected into COS cells, all of p73{alpha}, p73{alpha}(1–548), and p73{alpha}(1–427) localized in the cellular nucleus, whereas p73{alpha}(1–247) localized in both nucleus and cytoplasm. Intriguingly, when compared with p73{alpha}, both p73{alpha}(1–427) and p73{alpha}(1–548) showed a significant stimulation of the transcription of luciferase reporters harboring three p53-responsive promoters (p21Waf1, Mdm2, and Bax) in p53-deficient SAOS-2 cells. Gel retardation assays showed that DNA-binding activity of p73{alpha}(1–427) and p73{alpha}(1–548) was increased as compared with that of the full-length p73{alpha}. However, the colony formation assays using SAOS-2 cells demonstrated that, contrary to p73{alpha}, transfection of p73{alpha}(1–427) or p73{alpha}(1–548) resulted in no significant reduction of the number of colonies. These suggest that the distal COOH-terminal region of p73{alpha} is a cis- or trans-acting regulatory domain and regulates its functions diversely.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.