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Molecular adaptation to resistance exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
MyoD functions as a transcription factor that binds to ~60,000 MyoD DNA binding sites located all over the genome (91). Once bound to DNA, MyoD recruits acetyl- and methyltransferases that serve to open the DNA around muscle enhancer regions and then MyoD recruits more transcription factors to these enhancers driving the transcription of muscle-specific genes (92).
Molecular-Genetic Imaging
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Yannic Waerzeggers, Alexandra Winkeler, Andreas H. Jacobs
Several studies have shown that it is possible to image protein-protein interactions in vivo using PET (151) and optical techniques (152,153), as well as MRI (17). Ray et al. have used the two-hybrid system and modified it to be inducible. They used the NF-κB promoter to drive expression of two fusion proteins (VP16-MyoD and GAL4-Id), and modulated the NF-κB promoter through TNF-α. FLuc reporter gene expression was driven by the interaction of MyoD and Id through a transcriptional activation strategy. A similar strategy by Luker et al. involved interactions between the p53 tumor suppressor and the large T antigen of simian virus 40 (SV40). Specific binding of p53 to SV40 TAg induced expression of a reporter gene composed of a mutant HSV-1-tk fused to gfp. Byusing microPET imaging with [18F]FHBG the authors could detect binding of p53 and TAg in living mice and quantified a sixfold enhancement of tk activity in response to interaction of these two proteins in vivo in tumor xenografts of HeLa cells stably transfected with the imaging construct. In a proof-of-principle study De et al. demonstrated that BRET can be used for interrogating and observing protein-protein interactions directly at limited depths in living mice (153). They used the BRET2 system, which utilizes hRenilla luciferase protein and its protein DeepBlueC as an energy donor and a mutant GFP2 as the acceptor. These donor and acceptor proteins were fused to FKBP12 [the 12 kDa FK506 (=Tacrolimus) binding protein] and FRB [the rapamycin binding domain of FRAP (FKBP rapamycin-associated protein)], respectively, which are known to interact only in the presence of the small molecule mediator rapamycin. BRET2-specific GFP2 signal could only be detected in the presence of rapamycin, validating the use of BRET2 to noninvasively detect protein-protein interaction.
Regulation of Cell Functions
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
There is a tight coupling between cell cycle regulation and cell differentiation. In general, the terminal differentiation of cells is associated with their withdrawal from the cycle and the cessation of cell proliferation. A system studied in detail is represented by skeletal muscle development in vertebrates which partially depends on growth factor action.483 During development of muscle tissue, multipotential precursor cells proliferate extensively and progress through a myoblast stage before differentiating to become myocytes which requires withdrawal from the cell cycle. The onset of muscle cell differentiation is characterized by the expression of genes that code for muscle-specific enzymes, contractile proteins, and receptors that are not expressed in myoblasts. Expression of members of the MyoD family of myogenic regulatory genes is crucial for muscle differentiation.484 This family includes genes encoding MyoD, myogenin, Myf-5, and Myf-6. All of these gene products share a similar 57-amino acid basic helix-loop-helix (B-HLH) domain characterized by a strongly basic region and a potential HLH structure. Similar domains are found in an extended family of nuclear proteins which includes Myc proteins as well as some factors identified in Drosophila melanogaster. The structural similarity between the MyoD and Myc families is interesting because the c-Myc protein is implicated in the control of cell differentiation in many different biological systems. Cotransfection experiments have shown that expression of a c-myc gene can inhibit the differentiation of mouse NIH/3T3 fibroblasts made myogenic by the expression of a MyoD gene.485 MyoD and myogenin are not sufficient, acting alone or together, to drive muscle differentiation in the presence of high levels of c-Myc protein. The suppression produced by c-Myc can function independently of the activity of a negative regulator, termed Id, which would act through a different biochemical pathway. The Id protein contains an HLH domain but not an adjacent basic region. The Id protein can associate with MyoD and can inhibit its binding to DNA, and may negatively regulate the differentiation functions of tissue-specific B-HLH complexes by sequestering components of such complexes in inactive hetero-oligomers.486 These results indicate that whereas myogenic factors such as the members of the MyoD family act as positive regulators of muscle cell differentiation, c-Myc and Id may represent independent negative regulators of this process. It may be concluded that the molecular mechanisms of differentiation are very complex and are based on a balance between the actions of positive and negative regulatory molecules. Although the precise functions of these molecules are unknown, it seems likely that at least some of them act as direct or indirect regulators of the genetic program of the cell associated with the expression of certain differentiated functions.
History of Drosophila neurogenetic research in South Korea
Published in Journal of Neurogenetics, 2023
Greg S. B. Suh, Kweon Yu, Young-Joon Kim, Yangkyun Oh, Joong-Jean Park
As the primary interest of the field transitioned from early embryogenesis to tissue and organ development and pattern formation, South Korea witnessed the emergence of highly talented scientists who made critical contributions to the field. For example, Jaeseob Kim discovered that vestigial gene is required for wing development and, intriguingly, is sufficient to induce the development of wing tissues in any organ, such as eyes or legs, when it is expressed ectopically in these organs (Kim et al., 1996). Such a breakthrough led to further development of the concept of a ‘master regulator’ for organ development. Just as wing development was found to be governed by vestigial gene, Walter Gehring’s laboratory discovered that the development of eye is governed by eyeless gene (Halder, Callaerts, & Gehring, 1995). Just a half decade earlier, investigators had observed a simpler master regulator that was able to induce the development of a specific cell type. Myogenesis, for instance, was found to be induced by the expression of a single gene MyoD (Tapscott et al., 1988). It was not yet conceivable, however, that an entire organ consisting of different cell types could be induced and reconstituted through the ectopic expression of a single gene. This novel concept of the master regulator has influenced enormously – in the fields of mammalian development, stem cell, and organ regeneration years to come.
Muscle regeneration after high-dose radiation exposure: therapeutic potential of Hedgehog pathway modulation?
Published in International Journal of Radiation Biology, 2022
E. Rota Graziosi, S. François, J. Pateux, M. Gauthier, X. Butigieg, M. Oger, M. Drouet, D. Riccobono, N. Jullien
Muscle repair is a complex process that involves the regeneration of damaged fibers by new ones formed from particular stem cells identified in 1961 by Mauro and known as satellite cells (SC) (Mauro 1961; Zammit et al. 2006). These progenitors, interspersed between the plasma membrane and the basal layer of fibers, can be activated from their quiescent state following a traumatic event to proliferate and differentiate into mature myoblasts, which fuze to reconstitute myotubes. These newly-formed structures merge into myofibers and regenerate a functional muscle. The different stages of differentiation, fusion and maturation are orchestrated by a cascade of myogenic regulatory factors (MRF). SC markers Pax3 and Pax7 disappear after the early stages of activation. Then, in the intermediate stages, Myf5 and MyoD are necessary for myoblast commitment toward muscle cell differentiation. Myogenin (MyoG gene) plays a role in the late phases of fusion and in the synthesis of Myosin, essential for muscle functionality (Hawke and Garry 2001). Other mature proteins are also synthesized at the end of the process, such as beta-enolase (ENO3 gene) which is involved especially in the storage of glycogen.
Arsenic: an emerging role in adipose tissue dysfunction and muscle toxicity
Published in Toxin Reviews, 2022
Kaviyarasi Renu, Aditi Panda, Balachandar Vellingiri, Alex George, Abilash Valsala Gopalakrishnan
Myogenesis is a process classified into three major steps; withdrawal of myoblast from the cell cycle, expression of myotube-specific genes, and formation of multi-nucleated myotubes. The entire process of myogenesis is largely regulated by a group of transcription factors like Myogenic Differentiation Antigen (MyoD), myogenin, myogenic factor 5 (myf5), Muscle Regulatory Factor 4 (MRF4), myocyte enhancer factor which in turn regulates the expression of creatinine kinases and myosin heavy chain required for muscle production (Weintraub 1993, Lassar et al.1994, Olson et al.1995).