scholarly journals Root responses to aluminium and iron stresses require the SIZ1 SUMO ligase to modulate the STOP1 transcription factor

2021 ◽  
Author(s):  
Caroline Mercier ◽  
Brice Roux ◽  
Marien Have ◽  
Léa Le Poder ◽  
Nathalie Duong ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Sumo Ligase ◽  
Root Responses

scholarly journals Pax8 protein stability is controlled by sumoylation

2008 ◽  
Vol 42 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Tiziana de Cristofaro ◽  
Anna Mascia ◽  
Andrea Pappalardo ◽  
Barbara D'Andrea ◽  
Lucio Nitsch ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Critical Role ◽  
Nuclear Bodies ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Signal Transducers ◽  
Protein Protein Interaction ◽  
Sumo Ligase ◽  
Development And Differentiation ◽  
Substitution Mutant

The transcription factor Pax8 is involved in the morphogenesis of the thyroid gland and in the maintenance of the differentiated thyroid phenotype. Despite the critical role played by Pax8 during thyroid development and differentiation, very little is known of its post-translational modifications and how these modifications may regulate its activity. We focused our attention on the study of a specific post-translational modification, i.e., sumoylation. Sumoylation is a dynamic and reversible process regulating gene expression by altering transcription factor stability, protein–protein interaction and subcellular localization of target proteins. The analysis of Pax8 protein sequence revealed the presence of one sumoylation consensus motif (ψKxE), strongly conserved among mammals, amphibians, and fish. We demonstrated that Pax8 is sumoylated by the addition of a single small ubiquitin-like modifier (SUMO) molecule on its lysine residue 309 and that Pax8K309R, a substitution mutant in which the candidate lysine is replaced with an arginine, is no longer modified by SUMO. In addition, we analyzed whether protein inhibitor of activated signal transducers and activators of transcription (PIASy), a member of the PIAS STAT family of proteins, could function as a SUMO ligase and we demonstrated that indeed PIASy is able to increase the fraction of sumoylated Pax8. Interestingly, we show that Pax8 is targeted in the SUMO nuclear bodies, which are structures that regulate the nucleoplasmic concentration of transcription factors by SUMO trapping. Finally, we report here that the steady-state protein level of Pax8 is controlled by sumoylation.

CT7 (MAGE-C1) Promotes Survival and Interacts with STAT1 and PIASy in Multiple Myeloma Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1807-1807
Author(s):  
Tricia Nardiello ◽  
Anna Mei ◽  
Michael Mangone ◽  
Hearn J. Cho
Keyword(s):  
Multiple Myeloma ◽  
Transcription Factor ◽  
Ring Domain ◽  
Direct Result ◽  
Type I ◽  
Primary Cells ◽  
Myeloma Cells ◽  
Sumo Ligase ◽  
Bait Construct ◽  
Domain Protein

Abstract Abstract 1807 The type I Melanoma Antigen GEnes MAGE-A3 and CT7 (MAGE-C1) are detected in more than 75% of primary multiple myeloma specimens, and their expression is correlated with proliferation and progression of disease. We previously showed that MAGE-A3 inhibits apoptosis in human myeloma cell lines (HMCL) and primary cells in part through ubiquitinylation of the prototypical tumor suppressor p53, which targets it for proteasomal degradation and inhibits its pro-apoptotic transcriptional program (Nardiello et al, Clin Cancer Res, 2011; 17:4309). However, silencing of MAGE-A3 in HMCL and primary cells that lacked functional p53, either through deletions or mutations, also resulted in apoptosis. Silencing of CT7 alone did not affect survival of HMCL that lacked p53, but it did increase their sensitivity to chemotherapy-induced apoptosis. Many type I MAGE proteins, including MAGE-A3, bind to the RING domain protein TRIM28/Kap1 through their highly conserved MAGE Homology Domain (MHD) to form E3 ubiquitin ligase complexes, but it was unknown if CT7 also associated with TRIM28. These results lead to the hypothesis that CT7 is a survival factor for myeloma cells that can act through p53-independent mechanisms. To investigate the biochemical activity of CT7 and identify non-p53 pathways regulated by type I MAGE in myeloma cells, we analyzed protein-protein interactions with CT7 by two methods. We immunoprecipitated (IP'ed) CT7 from lysates of HMCL followed by sequencing of co-IP'ed proteins by mass spectroscopy and we performed yeast two-hybrid screening with a bait construct containing the MHD of CT7. CT7 was reciprocally co-IP'ed from HMCL lysates with TRIM28, demonstrating that it, too, associated with this RING domain protein. These methods also revealed two novel interactions with CT7. CT7 reciprocally co-IP'ed with STAT1, a transcription factor that plays a critical role in receptor-mediated signaling for cytokines such as interferon α/β. CT7 also interacted with Protein Inhibitor of Activated STAT y (PIASy), a modified RING domain protein that negatively regulates STAT proteins through its Small Ubiquitin-like MOdifier (SUMO) ligase activity, which sequesters target proteins out of the nucleus and into the cytoplasm. Surprisingly, phosphorylated STAT1 (pSTAT1) was detected in lysates from unstimulated HMCL, indicating a tonic level of activation, but most or all of the pSTAT1 was in the cytoplasm, suggesting that its transcriptional activity was being blocked through exclusion from the nucleus. Phospho-STAT1 also appeared to preferentially associate with the CT7/TRIM28 complex. Phospho-STAT1 did not appear to be ubiquitinylated in these HMCL, but SUMO2/3 modification of pSTAT1 was detected. These results suggest that CT7 negatively regulates pSTAT1 activity in HMCL by sequestering the transcription factor out of the nucleus through SUMO modification. This may be a direct result of CT7-mediated SUMOylation in partnership with PIASy, or indirectly due to CT7/TRIM28-mediated ubiquitinylation events that result in activation of a SUMO ligase such as PIASy. These findings suggest the possibility that complexes containing type I MAGE proteins may also have SUMO ligase activity and identify STAT1 as a novel non-p53 biochemical pathway regulated by these genes. Disclosures: No relevant conflicts of interest to declare.

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

2006 ◽  
Vol 282 (7) ◽  
pp. 4782-4793 ◽  
Author(s):  
James X. Du ◽  
C. Chris Yun ◽  
Agnieszka Bialkowska ◽  
Vincent W. Yang
Keyword(s):  
Transcription Factor ◽  
Rna Polymerase Ii ◽  
Cell Types ◽  
Luciferase Reporter ◽  
Physical Interaction ◽  
Intestinal Epithelial ◽  
Protein Inhibitor ◽  
Protein Levels ◽  
Sumo Ligase ◽  
Carboxyl Terminal

Krüppel-like factor 5 (KLF5) is a zinc finger-containing transcription factor that regulates proliferation of various cell types, including fibroblasts, smooth muscle cells, and intestinal epithelial cells. To identify proteins that interact with KLF5, we performed a yeast two-hybrid screen of a 17-day mouse embryo cDNA library with KLF5 as bait. The screen revealed 21 preys clustered in four groups as follows: proteins mediating gene expression, metabolism, trafficking, and signaling. Among them was protein inhibitor of activated STAT1 (PIAS1), a small ubiquitin-like modifier (SUMO) ligase that regulates transcription factors through SUMOylation or physical interaction. Association between PIAS1 and KLF5 was verified by co-immunoprecipitation. Structural determination showed that the acidic domain of PIAS1 bound to both the amino- and carboxyl-terminal regions of KLF5 and that this interaction was inhibited by the amino terminus of PIAS1. Indirect immunofluorescence demonstrated that PIAS1 and KLF5 co-localized to the nucleus. Furthermore, the PIAS1-KLF5 complex was co-localized with the TATA-binding protein and was enriched in RNA polymerase II foci. Transient transfection of COS-7 cells by PIAS1 and KLF5 significantly increased the steady-state protein levels of each other. Luciferase reporter and chromatin immunoprecipitation assays showed that PIAS1 significantly activated the promoters of KLF5 and PIAS1 and synergistically increased the transcriptional activity of KLF5 in activating the cyclin D1 and Cdc2 promoters. Importantly, PIAS1 increased the ability of KLF5 to enhance cell proliferation in transfected cells. These results indicate that PIAS1 is a functional partner of KLF5 and enhances the ability of KLF5 to promote proliferation.

scholarly journals Effects of the SUMO Ligase BCA2 on Metabolic Activity, Cell Proliferation, Cell Migration, Cell Cycle, and the Regulation of NF-κB and IRF1 in Different Breast Epithelial Cellular Contexts

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuhang Shi ◽  
Sergio Castro-Gonzalez ◽  
Yuexuan Chen ◽  
Ruth Serra-Moreno
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Cell Migration ◽  
Cell Lines ◽  
Metabolic Activity ◽  
Sumo Ligase ◽  
Breast Epithelial ◽  
The Impact

Breast cancer-associated gene 2 (BCA2) is an E3 ubiquitin and SUMO ligase with antiviral properties against HIV. Specifically, BCA2 (i) enhances the restriction imposed by BST2/Tetherin, impeding viral release; (ii) promotes the ubiquitination and degradation of the HIV protein Gag, limiting virion production; (iii) down-regulates NF-κB, which is necessary for HIV RNA synthesis; and (iv) activates the innate transcription factor IRF1. Due to its antiviral properties, ectopic expression of BCA2 in infected cells represents a promising therapeutic approach against HIV infection. However, BCA2 up-regulation is often observed in breast tumors. To date, the studies about BCA2 and cancer development are controversial, stating both pro- and anti-oncogenic roles. Here, we investigated the impact of BCA2 on cellular metabolic activity, cell proliferation, cell migration, and cell cycle progression. In addition, we also examined the ability of BCA2 to regulate NF-κB and IRF1 in transformed and non-tumor breast epithelial environments. Despite the fact that BCA2 promotes the transition from G1 to S phase of the cell cycle, it did not increase cell proliferation, migration nor metabolic activity. As expected, BCA2 maintains its enzymatic function at inhibiting NF-κB in different breast cancer cell lines. However, the effect of BCA2 on IRF1 differs depending on the cellular context. Specifically, BCA2 activates IRF1 in ER+ breast cell lines while it inhibits this transcription factor in ER– breast cancer cells. We hypothesize that the distinct actions of BCA2 over IRF1 may explain, at least in part, the different proposed roles for BCA2 in these cancers.

Author response for "Identification of Retinal Ganglion Cell Types and Brain Nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock‐in allele"

2020 ◽  
Author(s):  
Nadia Parmhans ◽  
Anne Drury Fuller ◽  
Eileen Nguyen ◽  
Katherine Chuang ◽  
David Swygart ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Cell Types ◽  
Cre Recombinase ◽  
Author Response ◽  
Retinal Ganglion ◽  
Brain Nuclei

Transcription factor/DNA interactions visualized by electron spectroscopic imaging

1992 ◽  
Vol 50 (1) ◽  
pp. 450-451
Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Phosphorus Content ◽  
Spectroscopic Imaging ◽  
Electron Spectroscopic Imaging ◽  
Dna Backbone ◽  
Two Parameters ◽  
High Level

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.

The role of transcription factor Egr‐1 in IL‐1 up‐regulation of tubular CD44 expression

Nephrology ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. A92-A92
Author(s):  
Takazoe K ◽  
Foti R ◽  
Hurst La ◽  
Atkins Rc ◽  
Nikolic‐Paterson DJ.
Keyword(s):  
Transcription Factor ◽  
Cd44 Expression

Alpha-fetoprotein producing gastric cancer cells lack transcription factor AT-motif binding factor 1 (ATBF1)

2001 ◽  
Vol 120 (5) ◽  
pp. A31-A31
Author(s):  
H KATAOKA ◽  
T JOH ◽  
T OHSHIMA ◽  
Y ITOH ◽  
K SENOO ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Alpha Fetoprotein ◽  
Gastric Cancer Cells ◽  
Binding Factor
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