Regulation of gene-activation pathways by PIAS proteins in the immune system

  title={Regulation of gene-activation pathways by PIAS proteins in the immune system},
  author={Ke Shuai and Bin Liu},
  journal={Nature Reviews Immunology},
  • K. ShuaiB. Liu
  • Published 1 August 2005
  • Biology
  • Nature Reviews Immunology
The protein inhibitor of activated STAT (PIAS) family of proteins has been proposed to regulate the activity of many transcription factors, including signal transducer and activator of transcription proteins (STATs), nuclear factor-κB, SMA- and MAD-related proteins (SMADs), and the tumour-suppressor protein p53. PIAS proteins regulate transcription through several mechanisms, including blocking the DNA-binding activity of transcription factors, recruiting transcriptional corepressors or co… 

Regulation of cytokine signaling pathways by PIAS proteins

The protein inhibitor of activated STAT (PIAS) protein family has been proposed to interact with over 60 proteins, many of which are transcription factors involved in the immune system.

A Role for Protein Inhibitor of Activated STAT1 (PIAS1) in Lipogenic Regulation through SUMOylation-independent Suppression of Liver X Receptors*

It is shown that PIAS1, a member of the protein inhibitor of the activated STAT family of proteins with small ubiquitin-like modifier (SUMO) E3 ligase activity, acts to suppress LXR ligand-dependent transcriptional activation of the lipogenic program in hepatocytes.

Identification of STAT3-independent regulatory effects for protein inhibitor of activated STAT3 by binding to novel transcription factors

This work develops models for STAT3 knockdown and PIAS3 over-expression and identifies novel transcription factor binding partners for PIas3 including ETS, EGR1, NR1I2, and GATA1, resulting in alterations in canonical pathways including Wnt/β-catenin signaling and functions such as cell death and proliferation.

Protein Inhibitor of Activated STAT1 Interacts with and Up-regulates Activities of the Pro-proliferative Transcription Factor Krüppel-like Factor 5*

Results indicate that PIAS1 is a functional partner of KLF5 and enhances the ability of KLf5 to promote proliferation in transfected cells.

Multiple Functions of Protein Inhibitor of Activated STAT1 in Regulating Endothelial Cell Proliferation and Inflammation.

  • J. Abe
  • Biology
    Arteriosclerosis, thrombosis, and vascular biology
  • 2016
The data suggest that in response to vascular endothelial growth factor-A and subsequent S100A6 induction, PIAS1 plays a crucial role in regulating endothelial proliferation, including inflammation, proliferation, and Kruppel like factor 2/endothelial nitric oxide synthase expression.

The Role of Signal Transducer and Activator of Transcription 3 (STAT3) and Its Targeted Inhibition in Hematological Malignancies

This review focuses on the role of STAT3 in pathogenesis i.e., proliferation, differentiation, migration, and apoptosis of hematological malignancies viz. leukemia, lymphoma and myeloma, and briefly highlights the potential therapeutic approaches developed against STAT3 activation pathway.

The Biological Functions of the Versatile Transcription Factors STAT3 and STAT5 and New Strategies for their Targeted Inhibition

The functions of STAT3 and STAT5 in different cell types and the strategies that are used to counteract their action in tumor cells are summarized.



PIAS/SUMO: new partners in transcriptional regulation

A model how the PIAS/ SUMO system may modulate transcriptional activities by mediating the assembly of coactivator or corepressor complexes within distinct subnuclear structures is proposed.

SUMO Modification of STAT1 and Its Role in PIAS-mediated Inhibition of Gene Activation*

It is demonstrated that STAT1 is a substrate for SUMO modification and that PIASx-α, but not PIAS1, functions as an E3 ligase to promote STAT1 modification, and that inhibition of STAT1 by PIAS proteins does not requiresumO modification ofSTAT1 itself.

Inhibition of Stat1-mediated gene activation by PIAS1.

  • B. LiuJ. Liao K. Shuai
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
The results identify PIAS1 as a specific inhibitor of Stat1-mediated gene activation and suggest that there may exist a specific PIAS inhibitor in every STAT signaling pathway.

Specific inhibition of Stat3 signal transduction by PIAS3.

Results indicate that PIAS3 is a specific inhibitor of Stat3, a signal transducer and activator of transcription-3 (Stat3) protein activated by the interleukin 6 family of cytokines, epidermal growth factor, and leptin.

Negative Regulation of NF-κB Signaling by PIAS1

It is reported here that PIAS1 (protein inhibitor of activated STAT1) is an important negative regulator of NF-κB, and microarray analysis indicates that the removal ofPIAS1 results in an increased expression of a subset of NF -κB-mediated genes in response to tumor necrosis factor alpha and lipopolysaccharide.

PIASx Is a Transcriptional Co-repressor of Signal Transducer and Activator of Transcription 4*

It is reported here that PIASx, a member of the protein inhibitor of activated STAT (PIAS) family, is a negative regulator of Stat4, a latent cytoplasmic transcription factor that becomes associated with Stat4 following IL-12 stimulation in vivo.

Modulation of STAT signaling by STAT-interacting proteins

The roles of STAT-interacting proteins in the regulation of STAT signaling are reviewed, finding a number of proteins function to modulate STAT signaling at various steps and mediate the crosstalk of STATs with other cellular signaling pathways.

Activation of p53 by Protein Inhibitor of Activated Stat1 (PIAS1)*

It is reported that protein inhibitor of activated Stat1 (PIAS1) interacts with the tetramerization and C-terminal regulatory domains of p53 in yeast two-hybrid analyses, suggesting that PIAS1 is a novel activator of p 53.

PIAS proteins promote SUMO-1 conjugation to STAT1.

It is shown that STAT1 is subject to SUMO-1 modification, and sumoylation occurs in vivo and in vitro at a single, evolutionary conserved amino acid residue Lys703, and that PIAS proteins promote SUMo-1 conjugation to STAT1.

STATs and gene regulation.

The discovery of a STAT in Drosophila, and most recently in Dictyostelium discoideum, implies an ancient evolutionary origin for this dual-function set of proteins.