Resolving the Combinatorial Complexity of Smad Protein Complex Formation and Its Link to Gene Expression.
نویسندگان
چکیده
Upon stimulation of cells with transforming growth factor β (TGF-β), Smad proteins form trimeric complexes and activate a broad spectrum of target genes. It remains unresolved which of the possible Smad complexes are formed in cellular contexts and how these contribute to gene expression. By combining quantitative mass spectrometry with a computational selection strategy, we predict and provide experimental evidence for the three most relevant Smad complexes in the mouse hepatoma cell line Hepa1-6. Utilizing dynamic pathway modeling, we specify the contribution of each Smad complex to the expression of representative Smad target genes, and show that these contributions are conserved in human hepatoma cell lines and primary hepatocytes. We predict, based on gene expression data of patient samples, increased amounts of Smad2/3/4 proteins and Smad2 phosphorylation as hallmarks of hepatocellular carcinoma and experimentally verify this prediction. Our findings demonstrate that modeling approaches can disentangle the complexity of transcription factor complex formation and its impact on gene expression.
منابع مشابه
Comparison of protective effect of two types of aerobic and intermittent training on breast cancer by TGFβ protein and Smad-3 gene and MMP2 in female mice
Introduction: The aim of this study was to compare the protective effects of two types of aerobic and intermittent training on breast cancer as a result of TGFβ protein, Smad-3, and MMP2 gene in female mice. Methods: In the experimental study, a total of 24 female BALB/c mice after Tumorigenesis by MC4-L2 cell line in the three groups; Control, Aerobic, and Intermittent training groups,...
متن کاملCooperativity in biological systems
Living organisms can sense and respond to external and internal stimuli. Response isdemonstrated in many forms including modulation of gene expression profiles, motility,secretion, cell death, etc. Nevertheless, all forms share a basic property: they depend on sensingsmall changes in the concentration of an effector molecule or subtle conformational changes ina protein and invoking the appropri...
متن کاملEffect of 4 Weeks of High Intensity Interval Training with Curcumin Supplementation on COL-I, COL- II, SMAD3 Gene Expression in the Myocardium of Obese Male Rats with Type 2 Diabetes
Introduction: The aim of this study was investigating the effect of 4 weeks of high intensity interval training with curcumin supplement on the gene expression of collagen I, II and SMAD/3 in the myocardium of male obese rats with type 2 diabetes. Methods: In this experimental study, 35 male diabetic rats were divided in to 5 groups of seven; normal control, diabetic control, curcumin+diabeti...
متن کاملComparison of the effects of two types of high intensity interval training on the gene expression of collagen 1, 2, and SMAD/3 in the left ventricle of male rats in type 2 diabetes induced by streptozotocin
Background and Objective: High-intensity interval training reduces diabetic cardiomyopathy by regulating gene expression in patients with diabetes. The aim of this study was to compare the effect of two types of high intensity interval training on the expression of collagen 1, 2 and SMAD/3 genes in the left ventricle of male rats with type 2 diabetes. Materials and Methods: The present study w...
متن کاملEffects of fibromodulin protein expression on NFkB and TGFβ signaling pathways in liver cancer cells
Introduction: The incidence rate of liver cancer is continuously increasing. Currently, gene therapy is applied to improve various medical issues such as cancer treatment approaches. Correspondingly, fibromodulin involves in many biological and physiological processes through interaction with growth factors and signaling pathway receptors. The aim of this study was to investigate the effects of...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cell systems
دوره 6 1 شماره
صفحات -
تاریخ انتشار 2018