PA28γ, an Accomplice to Malignant Cancer

Abstract

PA28g is a nuclear activator of the 20S proteasome, which is involved in the regulation of several essential cellular processes and angiogenesis. Over the past 20 years, many amino acid sites and motifs have been proven to play important roles in the characteristic functions of PA28g. The number of binding partners and validated cellular functions of PA28g have increased, which has facilitated the clarification of its involvement in different biological events. PA28g is involved in the progression of various diseases, and its aberrant overexpression in cancer is remarkable. Patients with low levels of PA28g expression have a higher survival rate than those with high levels of PA28g expression, as has been shown for a wide variety of tumors. The functions of PA28g in cancer can be divided into five main categories: cell proliferation, cell apoptosis, metastasis and invasion, cell nuclear dynamics that have relevance to angiogenesis, and viral infection. In this review, we focus on the role of PA28g in cancer, summarizing its aberrant expression, prooncogenic effects and underlying mechanisms in various cancers, and we highlight the possible cancer-related applications of PA28g, such as its potential use in the diagnosis, targeted treatment and prognostic assessment of cancer.

PA28γ: New Insights on an Ancient Proteasome Activator

“…PA28γ is overexpressed in several types of cancer [ 111 , 112 , 113 , 114 , 115 , 116 ] and on the basis of this observation its role as an oncoprotein that favors tumorigenesis is widely accepted [ 91 , 117 ]. In fact, its biological functions described in the previous paragraphs, and in particular its stimulating activity on cell growth and proliferation together with its ability to reduce apoptosis, can certainly justify, at least in part, its role in promoting tumor growth.…”

Identification of a BRAF/PA28γ/MEK1 signaling axis and its role in epithelial-mesenchymal transition in oral submucous fibrosis

“…Proteasomal activator 28 gamma (PA28γ) was first identified as a Ki antigen, a nucleoprotein targeted by autoantibodies found in the serum of patients with systemic lupus erythematosus [ 13 – 15 ]. Structurally, PA28γ differs from its family proteins PA28α and PA28β, which have unique biological characteristics [ 16 , 17 ].…”