RSK2 and its binding partners in cell proliferation, transformation and cancer development

Abstract

RSK2 is a serine/threonine kinase and a member of the p90 ribosomal S6 kinase (p90; RSKs) family, which regulates cell proliferation and transformation induced by tumor promoters such as epithelial growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate (TPA), and ultraviolet (UV) radiation. RSKs respond to many growth factors, hormones, neurotransmitters and environmental stresses. In signaling cascades, RSK2 is regulated under the control of extracellular signal-regulated kinase 1 (ERK1) and 2 (ERK2) activities and is positioned upstream of transcription and epigenetic factors involved in cell proliferation, cell transformation and cancer development, as well as some kinases that modulate cell cycle progression. Over the last decade, our research group has studied the etiological roles of RSK2 in human cancer development, discovering that RSK2 plays a key role in cell proliferation, transformation and cancer development in humans. Based on our research, we concluded that RSK2 plays a key role as an onco-kinase by combinational protein-protein interaction with different binding partners depending on the cellular context. In this review, we discuss the function of the RSK2 signaling axis by interactions with binding partners in cancer development.

Magnolin targeting of ERK1/2 inhibits cell proliferation and colony growth by induction of cellular senescence in ovarian cancer cells

“…To explore the anticancer activity of magnolin, we utilized several cancer cells including pancreatic cancer cells (AsPC‐1, BxPC‐3, Capan‐1, Capan‐2, and MIA PaCa‐2), colon cancer cells (SW480, HCT 116, HT‐29, and COLO 205), breast cancer cells (MCF7, MDA‐MB‐231, SKBR3, and BT‐474), and ovarian cancer cells (TOV‐112D and SKOV3). Since it has been reported that cancer cells originating from different organs or tissues harbor predominately different mutation(s) in different genes, we firstly analyzed mutations of oncogenes and tumor suppressor genes against the aforementioned cancer cell lines by searching the CCLE (https://portals.broadinstitute.org/ccle_legacy/home) mutaome database (Table ). The results showed that pancreatic cancer cells exhibited gain‐of‐function mutations, mainly in MAPK, and loss‐of‐function mutations, mainly in p16, p53, and SMAD4 (Table ).…”

Identification of p90 Ribosomal S6 Kinase 2 as a Novel Host Protein in HBx Augmenting HBV Replication by iTRAQ‐Based Quantitative Comparative Proteomics

“…The RSK (90 kDa ribosomal S6 kinase) family comprises a group of highly related serine/threonine kinases that regulate diverse cellular processes, including cell growth, proliferation, survival and motility . Members of this family, which are downstream effectors of the Ras/ERK signaling pathway, includes four vertebrate isoforms (RSK1, RSK2, RSK3, and RSK4) . RSK2 was identified as an important effector of ERK in global transcriptional regulation.…”

“…[12] Members of this family, which are downstream effectors of the Ras/ERK signaling pathway, includes four vertebrate isoforms (RSK1, RSK2, RSK3, and RSK4). [13] RSK2 was identified as an important effector of ERK in global transcriptional regulation. Indeed, activated RSK2 was shown to phosphorylate several transcription factors including AP-1, CREB, c-Fos, c-Jun, and others, some of which contribute to the IEG (immediate-early gene) response or are IEG products themselves.…”

Alpha 6 integrins promote cytokinesis by regulating the expression of RSK2 and MKLP1

“…Our published studies identified a role for integrins in the regulation of abscission (14) and have defined a role for ERK and its downstream target the ribosomal S6 kinase (RSK) (14). RSKs are a family of serine/threonine kinases that phosphorylate many cytoplasmic and nuclear targets (15)(16)(17). We previously demonstrated that depletion of either RSK1 or RSK2 in mammary epithelial cells inhibited cytokinesis (14), but did not determine whether both RSK isoforms were activated downstream of integrins or whether RSK1 and RSK2 regulated cytokinesis by similar or distinct mechanisms.…”