The Role of PIAS SUMO E3-Ligases in Cancer

Rabellino, Andrea; Andreani, Cristina; Scaglioni, Pier Paolo

doi:10.1158/0008-5472.can-16-2958

Cited by 90 publications

(85 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…PIAS E3‐ligases were initially described as transcriptional co‐regulators, but have been shown to play important roles in regulating protein stability and signal transduction through SUMOylation . There are four mammalian PIAS genes, which include: PIAS1 ; PIAS2 (also known as PIASx , with splice variants PIASx‐α and PIASx‐β ); PIAS3 (splice variant PIAS3β ); and PIAS4 (also known as PIASy , with a splice variant PIASyE6 − that lacks exon 6) . Among these, PIAS1 and PIAS4 have been extensively studied, and function in parallel by overlapping SUMO‐conjugation pathways to facilitate many cellular functions, but their substrate specificity is not well defined.…”

Section: Sumoylationmentioning

confidence: 99%

RNF4—A Paradigm for SUMOylation‐Mediated Ubiquitination

Kumar

Sabapathy

2019

Proteomics

View full text Add to dashboard Cite

Covalent modifications by Small Ubiquitin‐like MOdifier (SUMO) and ubiquitin conjugation are now recognized as independent posttranslational modifications (PTMs) employed by cells to reversibly regulate cellular signaling. SUMOylation in particular has emerged as a crucial cellular mechanism involved in multiple pathologies, including cancers, cardiovascular diseases, immunological and neurological disorders, as well as aging. Convergence of these two PTMs result in the ubiquitination of SUMOylated proteins, adding complexity in the modulation of protein functions. The SUMO‐Targeted Ubiquitin Ligases (STUbL) mediate this process, and RNF4, the mammalian STUbL, has been at the forefront in the understanding of this phenomenon. It has been shown to play important roles in a variety of cellular events, ranging from the maintenance of genomic integrity and hence, oncogenesis, to a role in development. Recent identification of direct and indirect RNF4 targets has revealed that the SUMOylation machinery is in itself targeted by RNF4, highlighting the complex nature of the signaling circuitry tightly regulating these processes. This review will touch upon both SUMOylation and ubiquitination, and will focus on how RNF4, which is at the heart of both these PTMs, modulates cellular signaling and promotes protein degradation. Moreover, the potential of therapeutically targeting RNF4 to improve cancer treatment is also explored.

show abstract

Section: Sumoylationmentioning

confidence: 99%

RNF4—A Paradigm for SUMOylation‐Mediated Ubiquitination

Kumar

Sabapathy

2019

Proteomics

View full text Add to dashboard Cite

show abstract

“…Both processes require three consecutive steps ( Fig. 18.1), sequentially catalysed by E1, E2 and E3 ligases (Swatek and Komander, 2016;Rabellino et al, 2017). While for ubiquitination, a variety of E1-3 ligases are known, for SUMOylation, only one E1 (SAE1/2) and one E2 (UBC9) are known, and only few classes of E3 ligases have been described so far, including RanBP2, PC2, TOPORS and the PIAS family (Rabellino et al, 2017).…”

Section: Ubiquitination and Sumoylation In Angiogenesismentioning

confidence: 99%

Roles of Ubiquitination and SUMOylation in the Regulation of Angiogenesis

Rabellino¹,

Andreani²,

Scaglioni³

2020

Current Issues in Molecular Biology

Self Cite

View full text Add to dashboard Cite

The generation of new blood vessels from the existing vasculature is a dynamic and complex mechanism known as angiogenesis. Angiogenesis occurs during the entire lifespan of vertebrates and participates in many physiological processes. Furthermore, angiogenesis is also actively involved in many human diseases and disorders, including cancer, obesity and infections. Several inter-connected molecular pathways regulate angiogenesis, and post-translational modifications, such as phosphorylation, ubiquitination and SUMOylation, tightly regulate these mechanisms and play a key role in the control of the process. Here, we describe in detail the roles of ubiquitination and SUMOylation in the regulation of angiogenesis.caister.com/cimb Curr.

show abstract

“…The negative regulator PIAS, also known as E3 SUMO (E3-type ligases for small ubiquitin-like modifier)-protein ligase PIAS, belongs to a family of transcription regulatory proteins that interact with STAT, NF-κB, p73, and p53 transcription factors to regulate immune responses (Shuai & Liu 2005), tumor development (Rabellino et al 2017), cell differentiation (Ghaffari 2014), proliferation, and apoptosis (Sudharsan & Azuma 2012). In mammals, four PIAS genes [PIAS1, PIAS2 (PIASx), PIAS3, and PIAS4 (PIASy)] encode seven proteins (PIAS2, PIAS3, and PIAS4 encode two protein isoforms each while PIAS1 encodes a single protein).…”

Section: Piasmentioning

confidence: 99%

JAK/STAT signaling in insect innate immunity

Bang

2019

Entomological Research

View full text Add to dashboard Cite

Lack of an adaptive strategy to combat infection creates opportunities for the innate immune system to guide invertebrate defense mechanisms. The innate immunity signaling cascades in invertebrates are elaborate, complex, and pathogen‐specific. Among invertebrates, the most extended repertoire of molecules that function in the regulatory signaling pathways has been observed in insects. This is highlighted by the fact that antimicrobial peptide (AMP) production against pathogens is orchestrated through diverse immune pathways, either independently or through cross‐talk mechanisms. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway coordinates immune responses from cytokines and regulates multiple homeostasis mechanisms in the host. That pathway has been implicated in the regulation of cell growth, differentiation, apoptosis, and inflammatory reactions. Many novel therapeutic interventions for tumors have been aimed at inhibitors of the JAK/STAT cascade. The regulatory pathway has much fewer components in Drosophila, and human homologs of almost all the critical pathway components and negative regulators have been identified. Loss‐of‐function mutation analysis and RNA interference‐based gene silencing modeling have produced functional characterization of the core components and negative regulators in Drosophila melanogaster, Aedes aegypti, and Anopheles gambiae, and in some hymenopteran and lepidopteran species. The genome‐wide analysis of the coleopteran species, Tribolium castaneum and Tenebrio molitor have been explored for elucidation of their JAK/STAT pathway regulatory components. Considering the promise of the JAK/STAT pathway in the mammalian model, the regulatory pathway in insects seems interesting especially for understanding pathogen surveillance mechanisms.

show abstract

The Role of PIAS SUMO E3-Ligases in Cancer

Cited by 90 publications

References 49 publications

RNF4—A Paradigm for SUMOylation‐Mediated Ubiquitination

RNF4—A Paradigm for SUMOylation‐Mediated Ubiquitination

Roles of Ubiquitination and SUMOylation in the Regulation of Angiogenesis

JAK/STAT signaling in insect innate immunity

Contact Info

Product

Resources

About