Significance of the pathogenic mutation T372R in the Yin Yang 1 protein interaction with <scp>DNA</scp> – thermodynamic studies

Nieborak, Anna; Górecki, Andrzej

doi:10.1002/1873-3468.12106

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…Surprisingly, labeling efficiency of cysteine variants was significantly higher for NTFs than for YY1s, regardless of the location of the engineered cysteine residue and labeling conditions, despite the full‐length protein contain zinc fingers, which are (may be) also subjected to labeling. These observations may indicate the presence of interactions between the N‐ and C‐terminal fragments of YY1, as postulated previously . Such interactions can restrict the access of the label to the introduced cysteine residues.…”

Section: Discussionsupporting

confidence: 70%

“…The only exception was the S14C mutant, when

r_{0}^{app}

values were greater for NTF than for YY1 in both tested salt concentrations. This discrepancy may indicate direct interactions between the N‐ and C‐terminal fragments of YY1, which have been postulated previously . The difference of the

r_{0}^{app}

values observed only for this mutation may indicate that the vicinity of the S14 residue is involved in the intramolecular interaction.…”

Section: Discussionmentioning

confidence: 46%

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Site‐directed fluorescence labeling of intrinsically disordered region of human transcription factor YY1: The inhibitory effect of zinc ions

Górka

Górecki

Dziedzicka-Wasylewska

2017

Protein Science

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Site-specific labeling of proteins with fluorescent dyes allows the study of protein structure and function using a wide variety of fluorescent techniques. However, specific labeling is not trivial in the case of proteins containing multiple cysteine residues. An example of such a protein is transcription factor Yin Yang 1, which comprises eight cysteine residues in four C2H2 type zinc fingers in the C-terminal region. Kinetic measurements of the labeling process allowed us to develop preparative labeling of three cysteine residues differently introduced to the N-terminal, disordered fragment of the protein. The protocol developed in the present study allows to prepare the protein with high recovery yield and high selectivity of the labeling. This was confirmed using proteolytic digestion and spectroscopic approach. The labeling process was significantly affected by the presence of zinc ions and was dependent on the localization of the engineered cysteine residue. This is the first known example of the use of cysteine metal protection and labeling (CyMPL) technology for the labeling of protein regions with no stable secondary structures.

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Section: Discussionsupporting

confidence: 70%

“…The only exception was the S14C mutant, when

r_{0}^{app}

r_{0}^{app}

values observed only for this mutation may indicate that the vicinity of the S14 residue is involved in the intramolecular interaction.…”

Section: Discussionmentioning

confidence: 46%

Site‐directed fluorescence labeling of intrinsically disordered region of human transcription factor YY1: The inhibitory effect of zinc ions

Górka

Górecki

Dziedzicka-Wasylewska

2017

Protein Science

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“…Mutation of threonine to arginine at 372 positions of YY1 had been shown to inhibit DNA binding of YY1. 33 Thus, we further examined GLUT3 transcriptional activity in HCT116 p53null cells overexpressing mutant YY1 T372R (Supplementary Figure S5A) We found that YY1 T372R overexpression could not significantly affect the luciferase activity of GLUT3 reporter ( Figure 5H), as well as its mRNA expression level ( Figure 5I), indicating that YY1 directly regulates GLUT3 transcription. Concomitantly, YY1 T372R could not upregulate glucose consumption and lactate production ( Supplementary Figure S5B,C).…”

Section: Yin Yang 1 Directly Affects Glucose Transporter 3 Transcrimentioning

confidence: 98%

Yin Yang 1 promotes the Warburg effect and tumorigenesis via glucose transporter GLUT3

Wang

Huang

et al. 2018

Cancer Science

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Cancer cells typically shift their metabolism to aerobic glycolysis to fulfill the demand of energy and macromolecules to support their proliferation. Glucose transporter (GLUT) family‐mediated glucose transport is the pacesetter of aerobic glycolysis and, thus, is critical for tumor cell metabolism. Yin Yang 1 (YY1) is an oncogene crucial for tumorigenesis; however, its role in tumor cell glucose metabolism remains unclear. Here, we revealed that YY1 activates GLUT3 transcription by directly binding to its promoter and, concomitantly, enhances tumor cell aerobic glycolysis. This regulatory effect of YY1 on glucose entry into the cells is critical for YY1‐induced tumor cell proliferation and tumorigenesis. Intriguingly, YY1 regulation of GLUT3 expression, and, subsequently, of tumor cell aerobic glycolysis and tumorigenesis, occurs p53‐independently. Our results also showed that clinical drug oxaliplatin suppresses colon carcinoma cell proliferation by inhibiting the YY1/GLUT3 axis. Together, these results link YY1's tumorigenic potential with the critical first step of aerobic glycolysis. Thus, our novel findings not only provide new insights into the complex role of YY1 in tumorigenesis but also indicate the potential of YY1 as a target for cancer therapy irrespective of the p53 status.

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“…Our research group established a protocol for robust production of active, recombinant YY1 protein (Golebiowski et al, 2011) as well as a sensitive, quantitative equilibrium assay for YY1-DNA interaction (Golebiowski et al, 2012). These methods previously allowed us to precisely analyze the effect of another YY1 mutation, T372R, which is recurrent in insulinomas, and proved it to affect YY1 binding to DNA in a sequence-specific way (Nieborak & Gorecki, 2016). In this paper, we analyzed the impact of D380Y mutation on YY1 structure and its interaction with DNA.…”

Section: Introductionmentioning

confidence: 99%

The effect of D380Y pathogenic mutation in human Yin Yang 1 on the protein’s structure and function

Figiel

Łakomska

Dziedzicka-Wasylewska

et al. 2020

Acta Biochim Pol

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Yin Yang 1 is a human transcription factor that controls a number of genes and takes part in the regulation of cell cycle, proliferation, differentiation, and neuronal development. Yin Yang 1 is composed of an N-terminal intrinsically disordered fragment and a C-terminal domain responsible for binding to DNA, composed of four zinc fingers. Recently, various alterations in the Yin Yang 1’s DNA binding domain were linked with an unexplained intellectual disability named Gabriele-de Vries syndrome. In this paper, a repetitively occurring substitution of aspartate-380 for tyrosine was analyzed to assess its impact on Yin Yang 1’s structure and DNA binding. The substitution was found to affect Yin Yang 1’s secondary and tertiary structure to a limited extent and to impair the specificity of its interaction with DNA.

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Significance of the pathogenic mutation T372R in the Yin Yang 1 protein interaction with DNA – thermodynamic studies

Cited by 8 publications

References 32 publications

Site‐directed fluorescence labeling of intrinsically disordered region of human transcription factor YY1: The inhibitory effect of zinc ions

Site‐directed fluorescence labeling of intrinsically disordered region of human transcription factor YY1: The inhibitory effect of zinc ions

Yin Yang 1 promotes the Warburg effect and tumorigenesis via glucose transporter GLUT3

The effect of D380Y pathogenic mutation in human Yin Yang 1 on the protein’s structure and function

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