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Institution

University of Texas Southwestern Medical Center

HealthcareDallas, Texas, United States
About: University of Texas Southwestern Medical Center is a healthcare organization based out in Dallas, Texas, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 39107 authors who have published 75242 publications receiving 4497256 citations. The organization is also known as: UT Southwestern & UT Southwestern Medical School.


Papers
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Journal ArticleDOI
TL;DR: The purification and identification of a transcription factor that recognizes the carbohydrate response element (ChRE) within the promoter of the L-type pyruvate kinase (LPK) gene is reported, suggesting a possible mode of glucose-responsive regulation.
Abstract: Carbohydrates mediate their conversion to triglycerides in the liver by promoting both rapid posttranslational activation of rate-limiting glycolytic and lipogenic enzymes and transcriptional induction of the genes encoding many of these same enzymes. The mechanism by which elevated carbohydrate levels affect transcription of these genes remains unknown. Here we report the purification and identification of a transcription factor that recognizes the carbohydrate response element (ChRE) within the promoter of the L-type pyruvate kinase (LPK) gene. The DNA-binding activity of this ChRE-binding protein (ChREBP) in rat livers is specifically induced by a high carbohydrate diet. ChREBP's DNA-binding specificity in vitro precisely correlates with promoter activity in vivo. Furthermore, forced ChREBP overexpression in primary hepatocytes activates transcription from the L-type Pyruvate kinase promoter in response to high glucose levels. The DNA-binding activity of ChREBP can be modulated in vitro by means of changes in its phosphorylation state, suggesting a possible mode of glucose-responsive regulation. ChREBP is likely critical for the optimal long-term storage of excess carbohydrates as fats, and may contribute to the imbalance between nutrient utilization and storage characteristic of obesity.

629 citations

Journal ArticleDOI
TL;DR: It is shown that mice lacking the protein lysyl oxidase–like 1 (LOXL1) do not deposit normal elastic fibers in the uterine tract post partum and develop pelvic organ prolapse, enlarged airspaces of the lung, loose skin and vascular abnormalities with concomitant tropoelastin accumulation.
Abstract: Elastic fibers are components of the extracellular matrix and confer resilience1. Once laid down, they are thought to remain stable2, except in the uterine tract where cycles of active remodeling occur3. Loss of elastic fibers underlies connective tissue aging and important diseases including emphysema4,5,6,7. Failure to maintain elastic fibers is explained by a theory of antielastase-elastase imbalance8, but little is known about the role of renewal. Here we show that mice lacking the protein lysyl oxidase–like 1 (LOXL1) do not deposit normal elastic fibers in the uterine tract post partum and develop pelvic organ prolapse, enlarged airspaces of the lung, loose skin and vascular abnormalities with concomitant tropoelastin accumulation. Distinct from the prototypic lysyl oxidase (LOX), LOXL1 localizes specifically to sites of elastogenesis and interacts with fibulin-5. Thus elastin polymer deposition is a crucial aspect of elastic fiber maintenance and is dependent on LOXL1, which serves both as a cross-linking enzyme and an element of the scaffold to ensure spatially defined deposition of elastin.

629 citations

Journal ArticleDOI
TL;DR: It is demonstrated in vivo that transformed cells and their progeny undergo infiltration and multilineage differentiation during tumorigenesis, thus identifying a pretumorigenic cell population.

628 citations

Journal ArticleDOI
TL;DR: It is found ultrasound alone has a low sensitivity to detect early stage HCC in patients with cirrhosis and addition of AFP to ultrasound significantly increases sensitivity of early HCC detection in clinical practice.

627 citations

Journal ArticleDOI
01 Dec 1993-Nature
TL;DR: This work has determined the crystal structure of the porcine inhibitor, which is the first three-dimensional structure of a protein containing leucine-rich repeats and represents a new class of α/β protein fold.
Abstract: Ribonuclease inhibitor is a cytoplasmic protein that tightly binds and inhibits ribonucleases of the pancreatic ribonuclease superfamily. The primary sequence of this inhibitor contains leucine-rich repeats (LRRs); these motifs are present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. In vivo, ribonuclease inhibitor may have a role in the regulation of RNA turnover in mammalian cells and in angiogenesis. To define the structural features of LRR proteins and to understand better the nature of the tight interaction of ribonuclease inhibitor with ribonucleases, we have determined the crystal structure of the porcine inhibitor. To our knowledge, this is the first three-dimensional structure of a protein containing LRRs and represents a new class of alpha/beta protein fold. Individual repeats constitute beta-alpha structural units that probably also occur in other proteins containing LRRs. The non-globular shape of the structure and the exposed face of the parallel beta-sheet may explain why LRRs are used to achieve strong protein-protein interactions. A possible ribonuclease-binding region incorporates the surface formed by the parallel beta-sheet and the beta alpha loops.

627 citations


Authors

Showing all 39410 results

NameH-indexPapersCitations
Eugene Braunwald2301711264576
Joseph L. Goldstein207556149527
Eric N. Olson206814144586
Craig B. Thompson195557173172
Thomas C. Südhof191653118007
Scott M. Grundy187841231821
Michael S. Brown185422123723
Eric Boerwinkle1831321170971
Jiaguo Yu178730113300
John J.V. McMurray1781389184502
Eric J. Nestler178748116947
John D. Minna169951106363
Yuh Nung Jan16246074818
Andrew P. McMahon16241590650
Elliott M. Antman161716179462
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023114
2022406
20215,247
20204,674
20194,094
20183,400