This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 99/4/372    most recent 01.RES.0000237389.40000.02v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zong, C. Articles by Ping, P. Search for Related Content PubMed PubMed Citation Articles by Zong, C. Articles by Ping, P. Related Collections Biochemistry and metabolism Related Article

(Circulation Research. 2006;99:372.)
© 2006 American Heart Association, Inc.

Molecular Medicine

Regulation of Murine Cardiac 20S Proteasomes

Role of Associating Partners

Chenggong Zong, Aldrin V. Gomes, Oliver Drews, Xiaohai Li, Glen W. Young, Beniam Berhane, Xin Qiao, Samuel W. French, Fawzia Bardag-Gorce, Peipei Ping

From the Departments of Physiology and Medicine (C.Z., A.V.G., O.D., X.L., G.W.Y., B.B., X.Q., P.P.), School of Medicine, University of California at Los Angeles; and the Department of Pathology and Medicine (S.W.F., F.B.-G.), Harbor-UCLA Medical Center, Torrance, Calif.

Correspondence to Peipei Ping, Department of Physiology, UCLA School of Medicine, MRL Building, Suite 1609 CVRL, 675 CE Young Dr, Los Angeles, CA 90095. E-mail pping{at}mednet.ucla.edu

See related article, pages 362–371

Our recent studies have provided a proteomic blueprint of the 26S proteasome complexes in the heart, among which 20S proteasomes were found to contain cylinder-shaped structures consisting of both and ß subunits. These proteasomes exhibit a number of features unique to the myocardium, including striking differences in post-translational modifications (PTMs) of individual subunits and novel PTMs that have not been previously reported. To date, mechanisms contributing to the regulation of this myocardial proteolytic core system remain largely undefined; in particular, little is known regarding PTM-dependent regulation of cardiac proteasomes. In this investigation, we seek to elucidate the function and regulation of 20S proteasome complexes in the heart. Functionally viable murine cardiac 20S proteasomes were purified. Tandem mass spectrometry analyses, combined with native gel electrophoresis, immunoprecipitation, and immunoblotting, revealed the identification of 2 previously unrecognized functional partners in the endogenous intact cardiac 20S complexes: protein phosphatase 2A (PP2A), and protein kinase A (PKA). Furthermore, our results demonstrated that PP2A and PKA profoundly impact the proteolytic function of 20S proteasomes: phosphorylation of 20S complexes enhances the peptidase activity of individual subunits in a substrate-specific fashion. Moreover, inhibition of PP2A or the addition of PKA significantly modified both the serine- and threonine-phosphorylation profile of proteasomes; multiple individual subunits of 20S (eg, 1 and ß2) were targets of PP2A and PKA. Taken together, these studies provide the first demonstration that the function of cardiac 20S proteasomes is modulated by associating partners and that phosphorylation may serve as a key mechanism for regulation.

Key Words: 20S proteasomes • mass spectrometry • phosphorylation • associating partners

Related Article:

Mapping the Murine Cardiac 26S Proteasome Complexes

Aldrin V. Gomes, Chenggong Zong, Ricky D. Edmondson, Xiaohai Li, Enrico Stefani, Jun Zhang, Richard C. Jones, Sheeno Thyparambil, Guang-Wu Wang, Xin Qiao, Fawzia Bardag-Gorce, and Peipei Ping
Circ. Res. 2006 99: 362-371. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				O. Tsukamoto, T. Minamino, and M. Kitakaze Functional alterations of cardiac proteasomes under physiological and pathological conditions Cardiovasc Res, September 4, 2009; (2009) cvp282v2. [Abstract] [Full Text] [PDF]

				H. Luo, J. Wong, and B. Wong Protein degradation systems in viral myocarditis leading to dilated cardiomyopathy Cardiovasc Res, August 6, 2009; (2009) cvp225v2. [Abstract] [Full Text] [PDF]

				W. M. Hassan, D. A. Merin, V. Fonte, and C. D. Link AIP-1 ameliorates {beta}-amyloid peptide toxicity in a Caenorhabditis elegans Alzheimer's disease model Hum. Mol. Genet., August 1, 2009; 18(15): 2739 - 2747. [Abstract] [Full Text] [PDF]

				A. V. Gomes, G. W. Young, Y. Wang, C. Zong, M. Eghbali, O. Drews, H. Lu, E. Stefani, and P. Ping Contrasting Proteome Biology and Functional Heterogeneity of the 20 S Proteasome Complexes in Mammalian Tissues Mol. Cell. Proteomics, February 1, 2009; 8(2): 302 - 315. [Abstract] [Full Text] [PDF]

				Z. P. Cai, Z. Shen, L. Van Kaer, and L. C. Becker Ischemic preconditioning-induced cardioprotection is lost in mice with immunoproteasome subunit low molecular mass polypeptide-2 deficiency FASEB J, December 1, 2008; 22(12): 4248 - 4257. [Abstract] [Full Text] [PDF]

				H. Lu, C. Zong, Y. Wang, G. W. Young, N. Deng, P. Souda, X. Li, J. Whitelegge, O. Drews, P.-Y. Yang, et al. Revealing the Dynamics of the 20 S Proteasome Phosphoproteome: A Combined CID and Electron Transfer Dissociation Approach Mol. Cell. Proteomics, November 1, 2008; 7(11): 2073 - 2089. [Abstract] [Full Text] [PDF]

				B.-Y. Kang, S. Tsoi, Shan Zhu, Shenghui Su, and H. H. Kay Differential Gene Expression Profiling in HELLP Syndrome Placentas Reproductive Sciences, March 1, 2008; 15(3): 285 - 294. [Abstract] [PDF]

				F. Zhang, A. J. Paterson, P. Huang, K. Wang, and J. E. Kudlow Metabolic Control of Proteasome Function Physiology, December 1, 2007; 22(6): 373 - 379. [Abstract] [Full Text] [PDF]

				O. Drews, R. Wildgruber, C. Zong, U. Sukop, M. Nissum, G. Weber, A. V. Gomes, and P. Ping Mammalian Proteasome Subpopulations with Distinct Molecular Compositions and Proteolytic Activities Mol. Cell. Proteomics, November 1, 2007; 6(11): 2021 - 2031. [Abstract] [Full Text] [PDF]

				J. Herrmann, L. O. Lerman, and A. Lerman Ubiquitin and Ubiquitin-Like Proteins in Protein Regulation Circ. Res., May 11, 2007; 100(9): 1276 - 1291. [Abstract] [Full Text] [PDF]

				C. Patterson, C. Ike, P. W. Willis IV, G. A. Stouffer, and M. S. Willis The Bitter End: The Ubiquitin-Proteasome System and Cardiac Dysfunction Circulation, March 20, 2007; 115(11): 1456 - 1463. [Abstract] [Full Text] [PDF]

				X. Wang and J. Robbins Heart Failure and Protein Quality Control Circ. Res., December 8, 2006; 99(12): 1315 - 1328. [Abstract] [Full Text] [PDF]

				M. Mayr, J. Zhang, A. S. Greene, D. Gutterman, J. Perloff, and P. Ping Proteomics-based Development of Biomarkers in Cardiovascular Disease: Mechanistic, Clinical, and Therapeutic Insights Mol. Cell. Proteomics, October 1, 2006; 5(10): 1853 - 1864. [Full Text] [PDF]

				S. R. Powell The Cardiac 26S Proteasome: Regulating the Regulator Circ. Res., August 18, 2006; 99(4): 342 - 345. [Full Text] [PDF]

				A. V. Gomes, C. Zong, R. D. Edmondson, X. Li, E. Stefani, J. Zhang, R. C. Jones, S. Thyparambil, G.-W. Wang, X. Qiao, et al. Mapping the Murine Cardiac 26S Proteasome Complexes Circ. Res., August 18, 2006; 99(4): 362 - 371. [Abstract] [Full Text] [PDF]