Deciphering the signaling mechanisms of β‐arrestin1 and β‐arrestin2 in regulation of cancer cell cycle and metastasis

Abstract

β‐Arrestins are ubiquitously expressed intracellular proteins with many functions which interact directly and indirectly with a wide number of cellular partners and mediate downstream signaling. Originally, β‐arrestins were identified for their contribution to GPCR desensitization to agonist‐mediated activation, followed by receptor endocytosis and ubiquitylation. However, current investigations have now recognized that in addition to GPCR arresting (hence the name arrestin). β‐Arrestins are adaptor proteins that control the recruitment, activation, and scaffolding of numerous cytoplasmic signaling complexes and assist in G‐protein receptor signaling, thus bringing them into close proximity. They have participated in various cellular processes such as cell proliferation, migration, apoptosis, and transcription via canonical and noncanonical pathways. Despite their significant recognition in several physiological processes, these activities are also involved in the onset and progression of various cancers. This review delivers a concise overview of the role of β‐arrestins with a primary emphasis on the signaling processes which underlie the mechanism of β‐arrestins in the onset of cancer. Understanding these processes has important implications for understanding the therapeutic intervention and treatment of cancer in the future.

β−Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives

“…As reviewed recently (Peterson and Luttrell, 2017), Ras-mediated activation of mitogenic ERK1/2 signaling, transactivation of EGF receptors, and cytoskeletal rearrangements represent three major cellular pathways or mechanisms through which β-arrestins can promote cell cycle progression. In line with these findings, many studies have shown that β-arrestins play a role in cancer initiation and progression (Aamna et al, 2022;Bagnato and Rosanò, 2019;Shukla and Dwivedi-Agnihotri, 2020;Tian et al, 2022). In the following, we will briefly review several recent studies in the β-arrestin/cancer field.…”

“…Many studies have shown that altered GPCR signaling can contribute to cancer progression at multiple levels (Arang and Gutkind, 2020). Since βarr1 and βarr2 are important regulators of GPCR activity, it is not surprising that these two proteins have been implicated in the pathogenesis of various types of cancer (Aamna et al, 2022;Bagnato and Rosanò, 2019;Shukla and Dwivedi-Agnihotri, 2020;Tian et al, 2022) (Fig. 3).…”

Total Synthesis of Natural Products using Gold Catalysis

“…In most circumstances, the desired natural products are the members of one or more biosynthetic classes that allocate the identical biosynthetic intermediate [39] . Furthermore, natural product and their structural analogs have played a crucial function in pharmacotherapy, particularly in the medication of cancer and infectious disorders [49–52] …”

“…[39] Furthermore, natural product and their structural analogs have played a crucial function in pharmacotherapy, particularly in the medication of cancer and infectious disorders. [49][50][51][52] In this review, we have highlighted the contribution of several gold-catalyzed reactions, reported from 2015 to 2021 for the total synthesis of natural products. The review has been classified into sections based on the distinct classes of goldcatalyzed reactions, Including tandem/cascade/domino reactions, glycosidations, hydroarylation, alkoxycyclization, cycloisomerization, biscyclopropanation, cycloaddition, metathesis, and oxidative cyclization.…”