China
Africa
Explore chapters and articles related to this topic
Proto-Oncogene and Onco-Suppressor Gene Expression
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
The SRE contained within the c-fos promoter is recognized by transcription factors.566 A 63- to 67-kDa protein, the serum response factor (SRF), specifically recognizes the SRE and mediates the regulation of c-fos expression exerted by serum factors.148 In serum-stimulated mouse fibroblasts, newly synthesized SRF is translocated to the nucleus, where it undergoes posttranslational modifications, including phosphorylations, capable of modifying the affinity of SRF for the specific DNA sequences represented by the SRE. There is a synergism between the SRF protein and a p62 factor, the ternary complex factor (TCF), in their interaction with the SRE.567 The TCF does not bind directly to SRE sequences but interacts with the SRF protein. Activation of the SRF depends on its phosphorylation by protein kinase C, which in turn is associated with phospholipase C-dependent generation of diacylglycerol.568 Casein kinase II can also activate c-fos gene expression through the phosphorylation of the SRF protein.569
Novel Intriguing Strategies Attenuating to Sarcopenia
Published in Chad Cox, Clinical Nutrition and Aging, 2017
Kunihiro Sakuma, Akihiko Yamaguchi
Several possible mechanisms for age-related muscle atrophy have been described; however, the precise contribution of each is unknown. Age-related muscle loss is a result of reductions in the size and number of muscle fibers [21] possibly due to a multifactorial process that involves physical activity, nutritional intake, oxidative stress, and hormonal changes [3, 22]. The specific contribution of each of these factors is unknown, but there is emerging evidence that the disruption of several positive regulators (Akt and serum response factor) of muscle hypertrophy with age is an important feature in the progression of sarcopenia [23–25]. In contrast, many investigators have failed to demonstrate an age-related enhancement in levels of common negative regulators [atrophy gene-1 (Atrogin-1), myostatin, and calpain] in senescent mammalian muscles [24, 25].
Leiomyosarcoma
Published in Dongyou Liu, Tumors and Cancers, 2017
The MYOCD gene (on 17p12) encodes myocardin (MYOCD), a transcriptional cofactor of serum response factor, that regulates smooth muscle differentiation and cell migration. It is the most overexpressed in leiomyosarcomas of the retroperitoneum. Further, gains at 1q21.3, 11q12.2-q12.3, 16p11.2, and 19q13.12 correlate to increased risk of death. Some leiomyosarcomas demonstrate high expression levels of muscle-associated genes, including CALD1, SLMAP, ACTG2, CFL2, MYLK, ACTA2, MBNL1, TPM1, PPP1R12A, DTNA, FZD6, PPP1R12A, CLIC4, CDC42EP3, BARD1, TPM1, RAB27A, MAP1B, and EDIL [4,5].
The role of microRNA in neuronal inflammation and survival in the post ischemic brain: a review
Published in Neurological Research, 2023
William A. Li, Aslan Efendizade, Yuchuan Ding
Cerebral ischemia induces neurogenesis and angiogenesis in adult human and rodent models, which have been studied in depth compared to stroke-induced oligodendrogenesis. Oligodendrocytes (OL), myelin-forming cells in the central nervous system, are vulnerable to cerebral ischemia. Loss of oligodendrocytes and their myelin impairs axonal function and is detrimental to functional recovery. As expected, the therapies that aim to prevent myelin loss or promote myelin regeneration are critical to neuronal survival and subsequent functional and cognitive recovery after ischemia. Serum response factor (SRF) plays a crucial role in the maturation of OL, and when SRF is inhibited, differentiation of oligodendrocyte progenitor cells is arrested [64,65]. Buller et al. demonstrated that ischemic stroke causes an up-regulation of SRF and down-regulation of miR-9 and miR-200b in OL white matter [64]. The same study also found that miR-9 and miR-200 target the SRF 3′-UTR directly and down-regulate the translation of SRF mRNA [64]. This indicates that miR-9 and miR-200b play an important role in stroke-induced SRF up-regulation in oligodendrocyte progenitor cells and mature oligodendrocytes, which ultimately affects oligodendrocyte progenitor cell differentiation. Most recent study has shown miR-9 is down-regulated in mice with MCAO brain and oxygen–glucose deprivation neurons. Elevation of miR-9 restored the neurological scores and reduced the infarct volume, brain water content and behavioral impairments [66].
A patent review of pharmaceutical and therapeutic applications of oxadiazole derivatives for the treatment of chronic diseases (2013–2021)
Published in Expert Opinion on Therapeutic Patents, 2022
Abbas Hassan, Abid Hussain Khan, Faiza Saleem, Haseen Ahmad, Khalid Mohammed Khan
Many growth factors like mitogens and chemotactic agents play a vital role in cell growth, migration, proliferation, and invasion. In tissue culture, the medium for growing cells generally contains serum (e.g. fetal bovine serum). The serum also stimulates the migration and invasion of cancer cells and fibroblasts. Robust activation in gene transcription occurs by the treatment of cells with serum through serum response factor (SRF). Cirrhosis, diabetic nephropathy, and heart failure are characterized by the excess deposition of cellular matrix or fibrosis. Tissue fibrosis causes systematic sclerosis and idiopathic pulmonary fibrosis. The inhibitors of Rho- and myocardin-related transcription factors and serum response factor (Rho/MRTF/SRF)-mediated gene transcription can be used for the treatment of cancer and fibrotic disease. Recently, novel 2,5-disubstituted 1,3,4-oxadiazole derivatives have been reported to inhibit Rho/MRTF/SRF-mediated gene transcription. The biological activity of the 1,3,4-oxadiazole derivatives was estimated in the SRE.L luciferase reporter assay. Compounds 21, 22, and 23 showed excellent potent activity having IC50 values 0.0012 nM, 0.019 nM, and 0.02 nM, respectively (Figure 9) [29].
Emerging role for the Serum Response Factor (SRF) as a potential therapeutic target in cancer
Published in Expert Opinion on Therapeutic Targets, 2022
Haleema Azam, Lisa Pierro, Martina Reina, William M Gallagher, Maria Prencipe
Serum Response Factor (SRF) is a ubiquitous transcription factor (TF) involved in several cellular processes, including cytoskeletal organization [1,2], cellular proliferation, cell differentiation and cell motility [3]. SRF’s relationship with its many cofactors and regulators makes it tissue specific with its function varying from cell-to-cell type. Several studies show that SRF expression is associated with an aggressive cancer phenotype, leading to worse outcome. This review focuses on SRF’s emerging role as a key contributor to three major hallmarks of cancer: promoting cell proliferation, resistance to cell death, and inducing invasion and metastases. A growing number of studies suggests that targeting the SRF pathway may overcome these hallmarks, representing a promising novel target for cancer therapy.