Sam68 Guest STARs in TNF-α Signaling

Kunkel, Gregory T.; Wang, Xiaodong

doi:10.1016/j.molcel.2011.07.004

Cited by 4 publications

(3 citation statements)

References 8 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sam68 has been shown to have a dual role as an RNA-binding protein and as a docking protein in different systems [ 8 ], participating in signal transduction of different receptors, such as insulin [ 26 ], leptin [ 27 ], T-cell receptor [ 53 ], as well as EGF [ 25 ], HGF/Met [ 54 ] or TNFR1 [ 55 ]. In addition, Sam68 has also been involved in posttranscriptional gene regulation [ 3 ], where some posttranscriptional modifications of Sam68 such us Tyr-phosphorylation [ 9 ], Ser/Thr phosphorylation [ 12 ], acetylation [ 14 ], methylation [ 13 ] or SUMOylation [ 15 ] may modify Sam68 ability to participate in some cellular events.…”

Section: Discussionmentioning

confidence: 99%

Sam68 Mediates the Activation of Insulin and Leptin Signalling in Breast Cancer Cells

Pérez-Pérez¹,

Sánchez-Jiménez²,

Vilariño-García³

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

Obesity is a well-known risk factor for breast cancer development in postmenopausal women. High insulin and leptin levels seem to have a role modulating the growth of these tumours. Sam68 is an RNA-binding protein with signalling functions that has been found to be overexpressed in breast cancer. Moreover, Sam68 may be recruited to insulin and leptin signalling pathways, mediating its effects on survival, growth and proliferation in different cellular types. We aimed to study the expression of Sam68 and its phosphorylation level upon insulin and leptin stimulation, and the role of Sam68 in the proliferative effect and signalling pathways that are activated by insulin or leptin in human breast adenocarcinoma cells. In the human breast adenocarcinoma cell lines MCF7, MDA-MB-231 and BT-474, Sam68 protein quantity and gene expression were increased upon leptin or insulin stimulation, as it was checked by qPCR and immunoblot. Moreover, both insulin and leptin stimulation promoted an increase in Sam68 tyrosine phosphorylation and negatively regulated its RNA binding capacity. siRNA was used to downregulate Sam68 expression, which resulted in lower proliferative effects of both insulin and leptin, as well as a lower activation of MAPK and PI3K pathways promoted by both hormones. These effects may be partly explained by the decrease in IRS-1 expression by down-regulation of Sam68. These results suggest the participation of Sam68 in both leptin and insulin receptor signaling in human breast cancer cells, mediating the trophic effects of these hormones in proliferation and cellular growth.

show abstract

Section: Discussionmentioning

confidence: 99%

Sam68 Mediates the Activation of Insulin and Leptin Signalling in Breast Cancer Cells

Pérez-Pérez¹,

Sánchez-Jiménez²,

Vilariño-García³

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…These latter were shown to phosphorylate Sam68 via ERK to facilitate CD44v5 splicing and HGF-dependent cell migration [ 64 , 65 ]. Sam68 also exhibits scaffolding functions in response to environmental stimuli, such as EGF [ 66 ], HGF [ 67 ], and TNF-alpha [ 68 ] upon binding to their respective receptor tyrosine kinases. Multiple studies highlighted the implication of Sam68 in mediating TNF-α/NF-kB axis activation to sustain pro-survival signals in different contexts [ 32 , 35 , 38 ].…”

Section: Sam68 Is a Multifunctional Protein Involved In Homeostasismentioning

confidence: 99%

Sam68 is a druggable vulnerability point in cancer stem cells

da Silva,

Yevdokimova,

Benoit

2023

Cancer Metastasis Rev

View full text Add to dashboard Cite

Sam68 (Src associated in mitosis of 68 kDa) is an RNA-binding and multifunctional protein extensively characterized in numerous cellular functions, such as RNA processing, cell cycle regulation, kinase- and growth factor signaling. Recent investigations highlighted Sam68 as a primary target of a class of reverse-turn peptidomimetic drugs, initially developed as inhibitors of Wnt/β-catenin mediated transcription. Further investigations on such compounds revealed their capacity to selectively eliminate cancer stem cell (CSC) activity upon engaging Sam68. This work highlighted previously unappreciated roles for Sam68 in the maintenance of neoplastic self-renewal and tumor-initiating functions. Here, we discuss the implication of Sam68 in tumorigenesis, where central findings support its contribution to chromatin regulation processes essential to CSCs. We also review advances in CSC-targeting drug discovery aiming to modulate Sam68 cellular distribution and protein-protein interactions. Ultimately, Sam68 constitutes a vulnerability point of CSCs and an attractive therapeutic target to impede neoplastic stemness in human tumors.

show abstract

“…Thus, Sam68 acts as a scaffold protein in response to activation of membrane-bound receptors and extracellular signaling pathways, such as the T-cell receptor [43,48,50–52], insulin receptor [45,53], leptin receptor [54–57], TNF-alpha [58], EGF [59] or HGF/Met signaling [60]. As happens with other RBPs, the interplay between kinases, Sam68 and target RNAs have been suggested in the dynamic regulation of gene expression according to cell signaling.…”

Section: Role Of Sam68 In Signalingmentioning

confidence: 99%

Role of Sam68 in Post-Transcriptional Gene Regulation

Sánchez-Jiménez

Sánchez-Margalet

2013

IJMS

View full text Add to dashboard Cite

The STAR family of proteins links signaling pathways to various aspects of post-transcriptional regulation and processing of RNAs. Sam68 belongs to this class of heteronuclear ribonucleoprotein particle K (hnRNP K) homology (KH) single domain-containing family of RNA-binding proteins that also contains some domains predicted to bind critical components in signal transduction pathways. In response to phosphorylation and other post-transcriptional modifications, Sam68 has been shown to have the ability to link signal transduction pathways to downstream effects regulating RNA metabolism, including transcription, alternative splicing or RNA transport. In addition to its function as a docking protein in some signaling pathways, this prototypic STAR protein has been identified to have a nuclear localization and to take part in the formation of both nuclear and cytosolic multi-molecular complexes such as Sam68 nuclear bodies and stress granules. Coupling with other proteins and RNA targets, Sam68 may play a role in the regulation of differential expression and mRNA processing and translation according to internal and external signals, thus mediating important physiological functions, such as cell death, proliferation or cell differentiation.

show abstract

Sam68 Guest STARs in TNF-α Signaling

Abstract: In this issue of Molecular Cell, Ramakrishnan and Baltimore (2011) identify Sam68 as a TNFR1 docking protein required for proper activation of TNF-α signaling.

Cited by 4 publications

References 8 publications

Sam68 Mediates the Activation of Insulin and Leptin Signalling in Breast Cancer Cells

Sam68 Mediates the Activation of Insulin and Leptin Signalling in Breast Cancer Cells

Sam68 is a druggable vulnerability point in cancer stem cells

Role of Sam68 in Post-Transcriptional Gene Regulation

Contact Info

Product

Resources

About