Transcription factor regulation by mechanical stress

University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA 19103, United States.
The international journal of biochemistry & cell biology (Impact Factor: 4.24). 02/2012; 44(5):728-32. DOI: 10.1016/j.biocel.2012.02.003
Source: PubMed

ABSTRACT New technologies and interest in cell mechanics are generating exciting new discoveries about how material properties and forces affect biological structure and function. Mechanical forces are transduced via a variety of mechanisms, recently beginning to be revealed, into signals capable of altering cell function and structure. Responses to physical stimuli occur at multiple levels, from changes in the structures of single proteins to global cascades capable of altering cell proliferation and differentiation. This review describes recent findings in which physical stimuli were shown to modulate transcription factor activity, including that of armadillo/β-catenin, serum response factor (SRF), yes-associated protein (YAP) and nuclear factor κB (NF-κB).


Available from: Melissa G Mendez, May 29, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The identification of different pools of cardiac progenitor cells resident in the adult mammalian heart opened a new era in heart regeneration as a means to restore the loss of functional cardiac tissue and overcome the limited availability of donor organs. Indeed, resident stem cells are believed to participate to tissue homeostasis and renewal in healthy and damaged myocardium although their actual contribution to these processes remain unclear. The poor outcome in terms of cardiac regeneration following tissue damage point out at the need for a deeper understanding of the molecular mechanisms controlling CPC behavior and fate determination before new therapeutic strategies can be developed. The regulation of cardiac resident stem cell fate and function is likely to result from the interplay between pleiotropic signaling pathways as well as tissue- and cell-specific regulators. Such a modular interaction-which has already been described in the nucleus of a number of different cells where transcriptional complexes form to activate specific gene programs-would account for the unique responses of cardiac progenitors to general and tissue-specific stimuli. The study of the molecular determinants involved in cardiac stem/progenitor cell regulatory mechanisms may shed light on the processes of cardiac homeostasis in health and disease and thus provide clues on the actual feasibility of cardiac cell therapy through tissue-specific progenitors.
    Frontiers in Physiology 07/2014; 5:219. DOI:10.3389/fphys.2014.00219
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mechanotransduction -the ability to output a biochemical signal from a mechanical input- is related to the initiation and progression of a broad spectrum of molecular events. Yet, the characterization of mechanotransduction lacks some of the most basic tools as, for instance, it can hardly be recognized by enrichment analysis tools, nor could we find any pathway representation. This greatly limits computational testing and hypothesis generation on mechanotransduction biological relevance and involvement in disease or physiological mechanisms. We here present a molecular map of mechanotransduction, built in CellDesigner to warrant that maximum information is embedded in a compact network format. To validate the map's necessity we tested its redundancy in comparison with existing pathways, and to estimate its sufficiency, we quantified its ability to reproduce biological events with dynamic simulations, using Signaling Petri Networks. Availability and Implementation: SMBL language map CONTACT: SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. © The Author (2014). Published by Oxford University Press. All rights reserved. For Permissions, please email:
    Bioinformatics 11/2014; DOI:10.1093/bioinformatics/btu776 · 4.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mechanobiology is an emerging field that investigates how living cells sense and respond to their physical surroundings. Recent interest in the field has been sparked by the finding that stem cells differentiate along different lineages based on the stiffness of the cell surroundings (Engler et al., 2006), and that metastatic behavior of cancer cells is strongly influenced by the mechanical properties of the surrounding tissue (Kumar and Weaver, 2009). Many questions remain about how cells convert mechanical information, such as viscosity, stiffness of the substrate, or stretch state of the cells, into the biochemical signals that control tissue function. Caenorhabditis elegans researchers are making significant contributions to the understanding of mechanotransduction in vivo. This review summarizes recent insights into the role of mechanical forces in morphogenesis and tissue function. Examples of mechanical regulation across length scales, from the single-celled zygote, to the intercellular coordination that enables cohesive tissue function, to the mechanical influences between tissues, are considered. The power of the C. elegans system as a gene discovery and in vivo quantitative bioimaging platform is enabling an important discoveries in this exciting field.
    Progress in molecular biology and translational science 01/2014; 126:281-316. DOI:10.1016/B978-0-12-394624-9.00012-9 · 3.11 Impact Factor