ABfinity™ Recombinant Rabbit Monoclonal Antibody validated to Mouse, Human, Rat and expected reactivity with human, mouse, Orangutan, equine, canine, chicken, zebrafish, and Xenopus. This antibody is validated for use in Western Blot, Immunohistochemistry, Immunofluorescence, and Flow Cytometry. PA28γ is encoded by the 10197 gene, also known as proteasome (prosome, macropain) activator subunit 3, PA28G, REG-GAMMA, PA28-gamma.
Proteasome activator 28 (PA28), also known as 11S regulator, is composed of two homologous subunits, alpha (α) and beta (β), that share ~ 50% amino acid identity (1). A separate but related protein, PA28gamma, was originally identified as Ki antigen from sera of patients with systemic lupus erythematosus (1-3). PA28α and PA28β are located primarily in the cytoplasm, whereas PA28γ is located in the nucleus (4,5). PA28 binds to the outer rings on both ends of the 20S proteasome to form a football-like structure (6,7). Binding of PA28 greatly stimulates multiple peptidase activities of the 20S proteasome in an ATP-independent reaction, but lacks the ability to degrade large protein substrates, suggesting that PA28 may cooperate with the 26 S proteasome in a sequential proteolytic pathway (8,9).
In addition to its nuclear localization, PA28γ differs from PA28α and PA28β in that it is not responsive to stimulation with IFN-γ (10). Experiments with mice lacking the PA28γ gene (Psme3) demonstrate that PA28γ may be involved in cell cycle control; although PA28γ is not essential for development, its absence causes retardation of cell proliferation and body growth (10). Abnormally high expression of PA28γ has been observed in thyroid cancer, particularly in regions of cancer cells where growth rate is accelerated (11) PA28γ interacts directly with Hepatitis C virus (HCV) core protein, which targets HCV for degradation (12), and with MEKK3, which phosphorylates PA28γ and increases its cellular levels (13). PA28γ also acts to increase resistance to apoptosis by promoting MDM2-mediated degradation of p53 (14).
Ahn JY, et al. (1995) Primary structures of two homologous subunits of PA28, a γ-interferon-inducible protein activator of the 20S proteosome. FEBS Lett 366:37-42.
Nikaido T, et al. (1990) Cloning and nucleotide sequence of cDNA for Ki antigen, a highly conserved nuclear protein detected with sera from patients with systemic lupus erythematosus. Clin Exp Immunol 79:209-214.
Tanahashi N, et al. (1997) Molecular properties of the proteasome activator PA28 family proteins and gamma-interferon regulation. Genes Cells 2:195-211.
Soza A, et al. (1997) Expression and subcellular localization of mouse 20S proteasome activator complex PA28. FEBS Lett 413:27-34.
Wojcik C, et al. (1998) Proteasome activator (PA28) subunits, alpha, beta and gamma (Ki antigen) in NT2 neuronal precursor cells and HeLa S3 cells. Eur J Cell Biol 77:151-160.
Baumeister W, et al. (1998) The Proteasome: Paradigm Review of a Self-Compartmentalizing Protease. Cell 92:367-380.
Gray CW, et al. (1994). PA28 activator protein forms regulatory caps on proteasome stacked rings. J. Mol. Biol. 236, 7–15.
Groll M, et al. (1997) Structure of 20S proteasome from yeast at 2.4 Å resolution. Nature 386:463-471.
Ma CP, et al. (1992) Identification, purification, and characterization of a protein activator (PA28) of the 20 S proteasome (macropain). J Biol Chem 267:10515-10523.
Murata S, et al. (1999) Growth Retardation in Mice Lacking the Proteasome Activator PA28γ. J Biol Chem 274:38211-38215.
Okamura T, et al. (2003) Abnormally high expression of proteasome activator-γ in thyroid neoplasm. J Clin Endocrinol Metab 88:1374-1383.
Suzuki, R. et al. (2009) Proteasomal turnover of hepatitis C virus core protein is regulated by two distinct mechanisms: a ubiquitin-dependent mechanism and a ubiquitin-independent but PA28gamma-dependent mechanism. J. Virol. 83:2389-92.
Hagemann C, et al. (2003) MEKK3 interacts with the PA28γ regulatory subunit of the proteasome Biochem J. 373:71-79.
Zhang, Z. et al. (2008) Proteasome activator PA28 gamma regulates p53 by enhancing its MDM2-mediated degradation. EMBO J. 27:852-64.