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Article: Interactions of CCAAT/enhancer-binding protein β with transcriptional coregulators.

Miller, Maria

2016 Volume 62, Issue 3, Page(s) 343–348

Abstract: CCAAT/enhancer-binding proteins (C/EBPs) are key regulators of numerous cellular processes, including cell proliferation, differentiation, and tumorigenesis. Their biological activities require interactions with several protein partners and the formation ...

Title translation	Oddziaływania pomiędzy białkiem β wiążącym sekwencję wzmacniającą CCAAT a regulatorami transkrypcyjnymi.
Abstract	CCAAT/enhancer-binding proteins (C/EBPs) are key regulators of numerous cellular processes, including cell proliferation, differentiation, and tumorigenesis. Their biological activities require interactions with several protein partners and the formation of functional multiprotein complexes involved in DNA repair and cell cycle control. Members of the family (C/EBPα, β, δ, ε, and γ) bind to common DNA sequence motifs as homo- or hetero-dimers and interact with other transcription factors to control transcription of a number of eukaryotic genes. Of particular interest is C/EBPβ, which binds to closed chromatin and acts as a pioneering factor for initiating tissue-specific gene expression at several promoters. This review focuses on intermolecular interactions that underlie C/EBPβ's ability to regulate chromatin accessibility and directs readers to general reviews describing transcription regulation in eukaryotes.
Language	English
Publishing date	2016
Publishing country	Poland
Document type	Journal Article ; Review
ZDB-ID	414019-9
ISSN	0032-5422
ISSN	0032-5422
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Article ; Online: Structural basis for cell type specific DNA binding of C/EBPβ: The case of cell cycle inhibitor p15INK4b promoter.

Lountos, George T / Cherry, Scott / Tropea, Joseph E / Wlodawer, Alexander / Miller, Maria

Journal of structural biology

2022 Volume 214, Issue 4, Page(s) 107918

Abstract: C/EBPβ is a key regulator of numerous cellular processes, but it can also contribute to tumorigenesis and viral diseases. It binds to specific DNA sequences (C/EBP sites) and interacts with other transcription factors to control expression of multiple ... ...

Abstract	C/EBPβ is a key regulator of numerous cellular processes, but it can also contribute to tumorigenesis and viral diseases. It binds to specific DNA sequences (C/EBP sites) and interacts with other transcription factors to control expression of multiple eukaryotic genes in a tissue and cell-type dependent manner. A body of evidence has established that cell-type-specific regulatory information is contained in the local DNA sequence of the binding motif. In human epithelial cells, C/EBPβ is an essential cofactor for TGFβ signaling in the case of Smad2/3/4 and FoxO-dependent induction of the cell cycle inhibitor, p15INK4b. In the TGFβ-responsive region 2 of the p15INK4b promoter, the Smad binding site is flanked by a C/EBP site, CTTAA•GAAAG, which differs from the canonical, palindromic ATTGC•GCAAT motif. The X-ray crystal structure of C/EBPβ bound to the p15INK4b promoter fragment shows how GCGC-to-AAGA substitution generates changes in the intermolecular interactions in the protein-DNA interface that enhances C/EBPβ binding specificity, limits possible epigenetic regulation of the promoter, and generates a DNA element with a unique pattern of methyl groups in the major groove. Significantly, CT/GA dinucleotides located at the 5'ends of the double stranded element maintain local narrowing of the DNA minor groove width that is necessary for DNA recognition. Our results suggest that C/EBPβ would accept all forms of modified cytosine in the context of the CpT site. This contrasts with the effect on the consensus motif, where C/EBPβ binding is modestly increased by cytosine methylation, but substantially decreased by hydroxymethylation.
MeSH term(s)	Humans ; CCAAT-Enhancer-Binding Protein-beta/genetics ; Epigenesis, Genetic ; Cell Cycle ; Cytosine ; DNA/genetics
Chemical Substances	CCAAT-Enhancer-Binding Protein-beta ; Cytosine (8J337D1HZY) ; DNA (9007-49-2)
Language	English
Publishing date	2022-11-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1032718-6
ISSN	1095-8657 ; 1047-8477
ISSN (online)	1095-8657
ISSN	1047-8477
DOI	10.1016/j.jsb.2022.107918
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Article: The early years of retroviral protease crystal structures.

Miller, Maria

Biopolymers

2010 Volume 94, Issue 4, Page(s) 521–529

Abstract: Soon after its discovery, the attempts to develop anti-AIDS therapeutics focused on the retroviral protease (PR)-an enzyme used by lentiviruses to process the precursor polypeptide into mature viral proteins. An urgent need for the three-dimensional ... ...

Abstract	Soon after its discovery, the attempts to develop anti-AIDS therapeutics focused on the retroviral protease (PR)-an enzyme used by lentiviruses to process the precursor polypeptide into mature viral proteins. An urgent need for the three-dimensional structure of PR to guide rational drug design prompted efforts to produce milligram quantities of this enzyme. However, only minute amounts of PR were present in the HIV-1 and HIV-2 viruses, and initial attempts to express this protein in bacteria were not successful. This review describes X-ray crystallographic studies of the retroviral proteases carried out at NCI-Frederick in the late 1980s and early 1990s and puts into perspective the crucial role that the total protein chemical synthesis played in unraveling the structure, mechanism of action, and inhibition of HIV-1 PR. Notably, the first fully correct structure of HIV-1 PR and the first cocrystal structure of its complex with an inhibitor (a substrate-derived, reduced isostere hexapeptide MVT-101) were determined using chemically synthesized protein. Most importantly, these sets of coordinates were made freely available to the research community and were used worldwide to solve X-ray structures of HIV-1 PR complexes with an array of inhibitors and set in motion a variety of theoretical studies. Publication of the structure of chemically synthesized HIV-1 PR complexed with MVT-101 preceded only by six years the approval of the first PR inhibitor as an anti-AIDS drug.
MeSH term(s)	Crystallography, X-Ray/history ; HIV Protease/chemistry ; HIV Protease/history ; HIV Protease Inhibitors/chemistry ; HIV Protease Inhibitors/history ; HIV-1/enzymology ; HIV-2/enzymology ; History, 20th Century ; Oligopeptides/chemistry ; Oligopeptides/history ; Protein Structure, Tertiary ; Structure-Activity Relationship
Chemical Substances	HIV Protease Inhibitors ; Oligopeptides ; MVT 101 (125552-93-4) ; HIV Protease (EC 3.4.23.-)
Language	English
Publishing date	2010-07-01
Publishing country	United States
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1123-x
ISSN	1097-0282 ; 0006-3525
ISSN (online)	1097-0282
ISSN	0006-3525
DOI	10.1002/bip.21387
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Article: The importance of being flexible: the case of basic region leucine zipper transcriptional regulators.

Miller, Maria

Current protein & peptide science

2009 Volume 10, Issue 3, Page(s) 244–269

Abstract: Large volumes of protein sequence and structure data acquired by proteomic studies led to the development of computational bioinformatic techniques that made possible the functional annotation and structural characterization of proteins based on their ... ...

Abstract	Large volumes of protein sequence and structure data acquired by proteomic studies led to the development of computational bioinformatic techniques that made possible the functional annotation and structural characterization of proteins based on their primary structure. It has become evident from genome-wide analyses that many proteins in eukaryotic cells are either completely disordered or contain long unstructured regions that are crucial for their biological functions. The content of disorder increases with evolution indicating a possibly important role of disorder in the regulation of cellular systems. Transcription factors are no exception and several proteins of this class have recently been characterized as premolten/molten globules. Yet, mammalian cells rely on these proteins to control expression of their 30,000 or so genes. Basic region:leucine zipper (bZIP) DNA-binding proteins constitute a major class of eukaryotic transcriptional regulators. This review discusses how conformational flexibility "built" into the amino acid sequence allows bZIP proteins to interact with a large number of diverse molecular partners and to accomplish their manifold cellular tasks in a strictly regulated and coordinated manner.
MeSH term(s)	Amino Acid Sequence ; Animals ; Basic-Leucine Zipper Transcription Factors/chemistry ; Basic-Leucine Zipper Transcription Factors/metabolism ; DNA/metabolism ; Humans ; Molecular Sequence Data ; Protein Folding ; Protein Structure, Tertiary ; Transcriptional Activation
Chemical Substances	Basic-Leucine Zipper Transcription Factors ; DNA (9007-49-2)
Language	English
Publishing date	2009-04-07
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	2045662-1
ISSN	1389-2037
ISSN	1389-2037
DOI	10.2174/138920309788452164
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Article ; Online: Automated TTF-1 Immunohistochemistry Assay for the Differentiation of Lung Adenocarcinoma Versus Lung Squamous Cell Carcinoma.

Cintrón, Rosa Vélez / Martínez, Andrés J / Jusino, Jo Ann / Conte-Miller, María / Mendoza, Adalberto

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2279, Page(s) 1–12

Abstract: Due to therapeutic advances, the subclassification of non-small cell lung carcinomas (NSCLC) between the adenocarcinomas and squamous cell carcinomas subtypes is essential for the practice of personalized and targeted medicine. The clinical management ... ...

Abstract	Due to therapeutic advances, the subclassification of non-small cell lung carcinomas (NSCLC) between the adenocarcinomas and squamous cell carcinomas subtypes is essential for the practice of personalized and targeted medicine. The clinical management for these two NSCLC subtypes is different due to their different molecular properties and histological origins. Immunohistochemistry (IHC) markers such is TTF-1 play a key role in the differentiation of lung adenocarcinomas and squamous cell carcinomas. However, immunohistochemistry is a complex process involving many critical steps and the reliability of results depends on the standardization of the assay as well as the appropriate interpretation. Different laboratories use different reagents and different IHC approaches for the detection of TTF-1 in lung cancer tumors. Here we describe an automated IHC protocol used in our laboratory for the detection of TTF-1 in formalin-fixed, paraffin-embedded (FFPE) tissue sections from lung tumors.
MeSH term(s)	Adenocarcinoma of Lung/diagnosis ; Adenocarcinoma of Lung/metabolism ; Adenocarcinoma of Lung/pathology ; Automation, Laboratory ; Carcinoma, Squamous Cell/diagnosis ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms/diagnosis ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Male
Language	English
Publishing date	2021-03-08
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1278-1_1
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Article ; Online: Automated Immunohistochemistry Assay for the Detection of Napsin-A in Formalin-Fixed Paraffin-Embedded Tissues from Lung Tumors.

Cintrón, Rosa Vélez / Jusino, Jo Ann / Conte-Miller, María / Martínez, Andrés J / Mendoza, Adalberto

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2279, Page(s) 23–33

Abstract: Immunohistochemistry (IHC) enables the selective detection of proteins in cells of formalin-fixed-paraffin-embedded (FFPE) tissue sections. This technique plays a key role in the identification and classification of primary lung cancer tumors through the ...

Abstract	Immunohistochemistry (IHC) enables the selective detection of proteins in cells of formalin-fixed-paraffin-embedded (FFPE) tissue sections. This technique plays a key role in the identification and classification of primary lung cancer tumors through the evaluation of the expression of the aspartic proteinase Napsin-A. However, immunohistochemistry is a complex process involving many critical steps and the lack of standardization as well as inappropriate analytical conditions may contribute to inconsistent results between laboratories. Automated immunohistochemistry addresses this issue by ensuring the quality and the reproducibility of the results among different laboratories. Here we describe an automated IHC protocol used in our laboratory for the detection of Napsin-A in FFPE lung tissue sections.
MeSH term(s)	Automation, Laboratory ; Humans ; Immunohistochemistry ; Lung Neoplasms/diagnosis ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Paraffin Embedding
Language	English
Publishing date	2021-03-08
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1278-1_3
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Book ; Online ; Thesis: Klinische Ergebnisse von fortgeschrittenen Plattenepithelkarzinomen der Bindehaut nach chirurgischer Therapie

Miller, Maria-Christina

2014

Author's details	von Maria-Christina Miller
Language	German
Size	Online-Ressource, lll.
Document type	Book ; Online ; Thesis
Thesis / German Habilitation thesis	Univ., Diss.--München, 2014
Database	Former special subject collection: coastal and deep sea fishing

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Article ; Online: Phospho-dependent protein recognition motifs contained in C/EBP family of transcription factors: in silico studies.

Miller, Maria

Cell cycle (Georgetown, Tex.)

2006 Volume 5, Issue 21, Page(s) 2501–2508

Abstract: CCAAT/enhancer-binding proteins (C/EBPs) are transcriptional regulators implicated in cell proliferation, differentiation, survival, and tumorigenesis. Their biological activities require interactions with several protein partners. This report presents ... ...

Abstract	CCAAT/enhancer-binding proteins (C/EBPs) are transcriptional regulators implicated in cell proliferation, differentiation, survival, and tumorigenesis. Their biological activities require interactions with several protein partners. This report presents insights from in silico analysis aimed at identifying phosphorylation-dependent protein recognition motifs in C/EBPs. (1) All C/EBP variants contain intrinsically disordered Ser/Thr- and Pro-rich segments with potential docking sites for WW and Polo-box domains of prolyl isomerase Pin1 and Polo-like kinases (Plks), respectively. (2) Consensus phosphorylation sequences for Plks are located in a highly conserved region of transactivation domains, suggesting that Plks might modulate transcriptional activities of C/EBPs in a cell cycle-dependent manner. (3) Phosphorylation at these positions, as well as at conserved Ser in the extended basic region, would create phosphoserine-containing motifs (pSXXF/Y/I/L), which could be recognized by BRCT repeats containing proteins such as the PAX-transactivation-domain-interacting protein (PTIP), and the breast cancer-associated protein (BRCA1). Proteins containing BRCT domains serve as scaffolds, mediating protein-protein interactions and formation of functional multiprotein complexes involved in DNA repair and cell cycle control. These findings add a new perspective to studies aimed at elucidation of molecular mechanisms underlying the diverse functions of C/EBPs.
MeSH term(s)	Amino Acid Motifs ; Amino Acid Sequence ; Animals ; CCAAT-Enhancer-Binding Proteins/metabolism ; CCAAT-Enhancer-Binding Proteins/physiology ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Models, Biological ; Molecular Sequence Data ; NIMA-Interacting Peptidylprolyl Isomerase ; Peptidylprolyl Isomerase/metabolism ; Phosphorylation ; Protein Folding ; Sequence Homology, Amino Acid ; Serine/chemistry ; Transcription Factors/metabolism
Chemical Substances	CCAAT-Enhancer-Binding Proteins ; NIMA-Interacting Peptidylprolyl Isomerase ; Transcription Factors ; Serine (452VLY9402) ; PIN1 protein, human (EC 5.2.1.8) ; Peptidylprolyl Isomerase (EC 5.2.1.8)
Language	English
Publishing date	2006-09-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.4161/cc.5.21.3421
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Article: DASH diet vs. DASH diet plus physical activity in older patients with type 2 diabetes and high blood pressure: A randomized clinical trial.

L P de Oliveira, Vanessa / de Freitas, Mauren M / P de Paula, Tatiana / Gubert, Mayara L / Miller, Maria E P / Schuchmann, Renata A / Souza, Karen L A / Viana, Luciana V

Nutrition and health

2022 , Page(s) 2601060221124201

Abstract: Background and aims: To evaluate the effect of lifestyle modification by adopting a DASH diet, with and without physical activity guidance, on blood pressure, glycemic control, lipid profile, weight, and body composition in older patients with type 2 ... ...

Abstract	Background and aims: To evaluate the effect of lifestyle modification by adopting a DASH diet, with and without physical activity guidance, on blood pressure, glycemic control, lipid profile, weight, and body composition in older patients with type 2 diabetes mellitus (T2DM) and hypertension. Methods and results: For this randomized clinical trial, we recruited patients aged 60 years or older with T2DM and uncontrolled hypertension. One group (DASH) received only DASH dietary guidance, while the other group (DASHPED) received dietary guidance and encouragement to walk with a pedometer. Outcomes of interest were (1) blood pressure, (2) physical activity, (3) weight, body mass index (BMI), and body composition, and (4) biochemical variables. Measurements were taken at baseline and 16 weeks after the intervention. We included 35 patients in the analysis. At the end of the study, the DASHPED group had an mean increase in physical activity of 1721 steps/day. Both groups displayed significantly reduced weight, BMI, and waking diastolic pressures on ambulatory blood pressure monitoring after the intervention. A trend of reduced sleeping diastolic pressure was found in the DASHPED group. Changes in weight, BMI, muscle mass, body fat, waist-hip ratio, glycemic control, lipid profile, and insulin sensitivity did not differ between the groups. Conclusion: There was no difference in outcomes between the group that only dieted and the group that also performed increased physical activity, despite a significant increase in exercise. This reinforces the importance of dietary changes in immediate blood pressure control.
Language	English
Publishing date	2022-09-16
Publishing country	England
Document type	Journal Article
ZDB-ID	603215-1
ISSN	2047-945X ; 0260-1060
ISSN (online)	2047-945X
ISSN	0260-1060
DOI	10.1177/02601060221124201
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Article: Prevalence of Sarcopenia and Association with Lifestyle Patterns in Patients with Type 2 Diabetes Mellitus (P01-025-19)

Paula, Tatiana de / Araujo, Karen / Freitas, Mauren de / Lopes, Vanessa / Miller, Maria Elisa / Viana, Luciana

Current developments in nutrition. 2019 June 13, v. 3, no. Supplement_1

2019

Abstract: The aim of the study was to establish the prevalence of sarcopenia and associated factors in elderly with type 2 diabetes (DM) in southern Brazil. A cross-sectional study was performed in 240 patients with type 2 DM. The diagnosis of sarcopenia was ... ...

Abstract	The aim of the study was to establish the prevalence of sarcopenia and associated factors in elderly with type 2 diabetes (DM) in southern Brazil. A cross-sectional study was performed in 240 patients with type 2 DM. The diagnosis of sarcopenia was performed according to EWGSOP criteria. Muscle mass was calculated by skeletal muscle mass index (appendicular skeletal muscle mass/height2 - Inbody® bioimpendance). Muscle strength was assessed by manual grip strength (Jamar® dynamometer) and physical performance was assessed by the sit and lift test. Patients with type 2 DM with age ≥60 years and with the ability to ambulate were selected. Patients with recent cardiovascular events, serum creatinine >2.0 mg/dl, use of corticosteroids and BMI >40 kg/m2 were excluded. The sample size was 240 patients based on meta-analysis who found 17% sarcopenia in elderly patients without DM. We included 240 patients aged 68.4 ± 5.5 years, 53.2% were women and the duration of DM was 15 (8–22) years, the BMI was 29.4 ± 4.4 kg/m2. The prevalence of sarcopenia was 21% and men had more sarcopenia (75%). Patients with sarcopenia walk less [3541 (2227–4574) vs. 4521 (3037–5678) steps, P = 0.013], drink more alcohol [21 (56.8%) vs. 71 (31.8%); P < 0.034] and have lower total cholesterol levels [146 ± 41 Vs. 168 ± 43; P = 0.007] than the group without sarcopenia. In multivariate logistic regression models, walking < 3760 steps [OR = 2868; CI 95% 1.331–6.181] and male [OR = 5285; CI 95% 2261–12,350], were associated with sarcopenia. The prevalence of sarcopenia was 21%, higher than in patients without diabetes (17%). In this group of patients, lower physical activity, and male sex were associated with sarcopenia. FIPE n. 160467; CAPES.
Keywords	adrenal cortex hormones ; blood serum ; body mass index ; cholesterol ; creatinine ; cross-sectional studies ; elderly ; lifestyle ; males ; men ; meta-analysis ; muscle strength ; noninsulin-dependent diabetes mellitus ; patients ; regression analysis ; sarcopenia ; skeletal muscle ; walking ; women ; Brazil
Language	English
Dates of publication	2019-0613
Publishing place	Oxford University Press
Document type	Article
ISSN	2475-2991
DOI	10.1093/cdn/nzz028.P01-025-19
Database	NAL-Catalogue (AGRICOLA)

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