A comprehensive and perspective view of oncoprotein SET in cancer

Abstract

SET is a multifunctional oncoprotein which is ubiquitously expressed in all kinds of cells. The SET protein participates in many cellular processes including cell cycle, cell migration, apoptosis, transcription, and DNA repair. Accumulating evidence demonstrates that the expression and activity of SET correlate with cancer occurrence, metastasis, and prognosis. Therefore, the SET protein is regarded as a potential target for cancer therapy and several inhibitors are being developed for clinical use. Herein, we comprehensively review the physiological and pathological functions of SET as well as its structure‐function relationship. Additionally, the regulatory mechanisms of SET at both transcriptional and posttranslational levels are also discussed.

Embryonic Stem Cell Differentiation Is Regulated by SET through Interactions with p53 and β-Catenin

“…SET depletion is embryonically lethal ( Edupuganti et al., 2017 ; Kon et al., 2019 ), indicating that SET plays a crucial role in early development. Furthermore, although SET is highly conserved in nature and significantly expressed in the early embryo ( Bayarkhangai et al., 2018 ), the precise role of SET in regulating early differentiation and pluripotency has not yet been adequately addressed.…”

“…For example, Aurora kinase A (AURKA) phosphorylates p53 ( Lee et al., 2012 ) and GSK3β phosphorylates β-catenin ( Q.-L. Ying et al., 2008 ) while also regulating the pluripotent state of mESCs. Adding another layer of complexity, SET itself was shown to undergo phosphorylation ( Bayarkhangai et al., 2018 ; Yin et al., 2019 ) and was shown to interact with acetylated p53 ( Wang et al., 2016 ). Unlike AURKA or GSK3β, SET has not been reported to possess kinase activity or methyltransferase activity and is not directly involved in catalyzing PTMs.…”

TAF‑Iβ deficiency inhibits proliferation and promotes apoptosis by rescuing PP2A and inhibiting the AKT/GSK‑3β pathway in leukemic cells

“…The upregulation of TAF-Iβ has been detected in several solid tumors and has been associated with increased invasion and poor outcome (20). In addition, TAF-Iβ deficiency has been shown to decrease cell growth in various types of cancer (21); however, this does not occur in all types of tumor.…”

“…Regarding the mechanism suppressing the development of leukemia, the most commonly reported in the literature is the rescue of PP2A phosphatase activity (20). It is well known that PP2A is a serine/threonine phosphatase and acts as a tumor suppressor.…”

New Cytotoxic Cerebrosides from the Red Sea Cucumber Holothuria spinifera Supported by In-Silico Studies

“…Based on molecular modeling, the compounds exhibited their anti-tumor activity through targeting the PP2A inhibitor, SET. Overexpression of the SET oncoprotein was reported in breast cancer cell lines, including MCF-7 [58,59]. The use of SET antagonists and PP2A activators was postulated as a relatively novel strategy for breast cancer therapy [59].…”