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(Circulation Research. 2006;99:342.)
© 2006 American Heart Association, Inc.

Editorials

The Cardiac 26S Proteasome

Regulating the Regulator

Saul R. Powell

From The Feinstein Institute for Medical Research, Long Island Jewish Medical Center Campus, New Hyde Park; and Department of Medicine, The Albert Einstein College of Medicine, Bronx, NY.

Correspondence to Saul R. Powell, PhD, FAHA, Department of Medicine, Long Island Jewish Medical Center, 270-05 76th Ave, Rm B-387, New Hyde Park, NY 11042. E-mail spowell@lij.edu

See related articles, pages 362–371 and 372–380

Key Words: cardiac • ubiquitin–proteasome system • regulation • immunoproteasome • phosphorylation

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Significance of Ubiquitin–Proteasome–Mediated Degradation of Proteins

 
The ubiquitin–proteasome system (UPS) is the main pathway for the nonlysosomal degradation of intracellular proteins, representing upwards of 80% of all intracellular proteins. A key component of the UPS is the 26S proteasome, a macromolecular multisubunit complex that has the responsibility of recognizing, unfolding, and the ultimately destroying proteins that have been tagged by polyubiquitin chains generally at the -NH₂ group of an internal substrate lysine residue. This is a multistep process that has been reviewed in detail elsewhere.^1,2 What has become clear is that the rapid destruction of these proteins, some with high biological activity, actually represents a form of regulation of cellular processes. The UPS is now recognized as a regulator of the cell cycle and cell division,³ immune response and antigen presentation,⁴ apoptosis,⁵ and cell signaling.^6,7 Moreover, the UPS plays critical roles in protein quality by removal of damaged, oxidized, and/or misfolded proteins.^8,9 Ciechanover et al¹⁰ have aptly referred to this process as "biological regulation via destruction." Over the past few years, it has become increasingly clear that this critical regulatory system becomes dysfunctional in certain disease states, such as Alzheimer’s disease, Huntingdon’s disease, and amyotrophic lateral sclerosis.¹¹ With respect to the cardiovascular system, recent studies have suggested that myocardial ischemia,^12,13 certain mutant protein–associated cardiomyopathies,¹⁴ atherosclerosis,¹⁵ and even diabetes¹⁶ may be examples of proteasomal dysfunction disorders.

Despite all of the evidence supporting the critical role that the UPS plays in these processes, little is know about how the 26S proteasome itself is regulated. The majority of studies . . . [Full Text of this Article]

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]

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