+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Multifaceted interactions and regulation between antizyme and its interacting proteins cyclin D1, ornithine decarboxylase and antizyme inhibitor



Multifaceted interactions and regulation between antizyme and its interacting proteins cyclin D1, ornithine decarboxylase and antizyme inhibitor



Oncotarget 6(27): 23917-23929



Ornithine decarboxylase (ODC), cyclin D1 (CCND1) and antizyme inhibitor (AZI) promote cell growth. ODC and CCND1 can be degraded through antizyme (AZ)-mediated 26S proteasomal degradation. This paper describes a mechanistic study of the molecular interactions between AZ and its interacting proteins. The dissociation constant (Kd) of the binary AZ-CCND1 complex and the respective binding sites of AZ and CCND1 were determined. Our data indicate that CCND1 has a 4-fold lower binding affinity for AZ than does ODC and an approximately 40-fold lower binding affinity for AZ than does AZI. The Kd values of AZ-CCND1, AZ-ODC and AZ-AZI were 0.81, 0.21 and 0.02 μM, respectively. Furthermore, the Kd values for CCND1 binding to the AZ N-terminal peptide (AZ34-124) and AZ C-terminal peptide (AZ100-228) were 0.92 and 8.97 μM, respectively, indicating that the binding site of CCND1 may reside at the N-terminus of AZ, rather than the C-terminus. Our data also show that the ODC-AZ-CCND1 ternary complex may exist in equilibrium. The Kd values of the [AZ-CCND1]-ODC and [AZ-ODC]-CCND1 complexes were 1.26 and 4.93 μM, respectively. This is the first paper to report the reciprocal regulation of CCND1 and ODC through AZ-dependent 26S proteasomal degradation.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 058357430

Download citation: RISBibTeXText

PMID: 26172301


Related references

Regulation of hepatic ornithine decarboxylase by antizyme and antizyme inhibitor. Bachrach, U , A Kaye And R Chayen (Ed ) Advances in Polyamine Research, Vol 4 41st Bat-Sheva Seminar on Polyamines in Growth And Differentiation Processes, Kiryat Anavim, Jerusalem, Israel, July 4-9, 1982 Xxiv+808p Raven Press: New York, N Y , Usa Illus P683-692, 1983

Minimal antizyme peptide fully functioning in the binding and inhibition of ornithine decarboxylase and antizyme inhibitor. Plos one 6(9): E24366, 2011

Degradation of antizyme inhibitor, an ornithine decarboxylase homologous protein, is ubiquitin-dependent and is inhibited by antizyme. Journal of Biological Chemistry 279(52): 54097-54102, 2004

Critical factors governing the difference in antizyme-binding affinities between human ornithine decarboxylase and antizyme inhibitor. Plos one 6(4): E19253, 2011

Antizyme inhibitor is rapidly induced in growth-stimulated mouse fibroblasts and releases ornithine decarboxylase from antizyme suppression. Biochemical Journal 346 Pt 3: 699-704, 2000

Antizyme and antizyme inhibitor of ornithine decarboxylase (rat liver). Methods in Enzymology 94: 185-193, 1983

Docking of antizyme to ornithine decarboxylase and antizyme inhibitor using experimental mutant and double-mutant cycle data. Journal of Molecular Biology 390(3): 503-515, 2009

Nuclear translocation of antizyme and expression of ornithine decarboxylase and antizyme are developmentally regulated. Developmental Dynamics 220(3): 259-275, 2001

Existence of antizyme and ornithine decarboxylase-antizyme complex in RK13 kidney cells. Febs Letters 199(1): 49-52, 1986

Discovery of a spermatogenesis stage-specific ornithine decarboxylase antizyme: antizyme 3. Proceedings of the National Academy of Sciences of the United States of America 97(9): 4808-4813, 2000

Regulation of ornithine decarboxylase by antizymes and antizyme inhibitor in zebrafish (Danio rerio). Biochimica et Biophysica Acta 1578(1-3): 21-28, 2002

Stable siRNA-mediated silencing of antizyme inhibitor: regulation of ornithine decarboxylase activity. Biochemical and Biophysical Research Communications 328(1): 206-212, 2005

A macromolecular inhibitor of the antizyme to ornithine decarboxylase. Biochemical Journal 204(3): 647-652, 1982

Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase. Biochemical Journal 409(1): 187-192, 2008

Mouse ornithine decarboxylase-like gene encodes an antizyme inhibitor devoid of ornithine and arginine decarboxylating activity. Journal of Biological Chemistry 281(41): 30896-30906, 2006