Antizyme inhibitor: mysterious modulator of cell proliferation |
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Authors: | U Mangold |
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Institution: | (1) Program in Vascular Biology, Children’s Hospital, Karp Family Building, 1 Blackfan Circle, Boston, Massachusetts 02115, USA;(2) Department of Surgery, Harvard Medical School, Boston, Massachusetts 02115, USA |
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Abstract: | In contrast to the considerable interest in the oncogene ornithine decarboxylase (ODC) and in the family of antizymes with
regard to cell proliferation and tumorigenesis, the endogenous antizyme inhibitor (AZI) has been less well studied. AZI is
highly homologous to the enzyme ODC but does not possess any decarboxylase activity. Elevated ODC activity is associated with
most forms of human malignancies. Antizymes bind ODC, inhibit ODC activity and promote the ubiquitin-independent degradation
of ODC. Consequently they are proposed as tumor suppressors. In particular, the most studied member of the antizyme family,
antizyme 1, has been demonstrated to play a role in tumor suppression. AZI inactivates all members of the antizyme family,
reactivates ODC and prevents the proteolytic degradation of ODC, which may suggest a role for AZI in tumor progression.
Received 9 December 2005; received after revision 13 April 2006; accepted 1 June 2006 |
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Keywords: | Antizyme inhibitor antizyme polyamines ODC proteasome cancer |
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