China
Africa
Explore chapters and articles related to this topic
Transforming Growth Factor-α and Epidermal Growth Factor
Published in Jason Kelley, Cytokines of the Lung, 2022
Another indirect line of evidence linking the EGF family of growth factors to morphogenesis is the striking sequence homology that they share with homeotic genes of lower eukaryotes. For example, the drosophila homeotic gene Notch, which is essential for differentiation of the ectoderm into neural and epidermal tissues, contains 36 EGF-like repeats within its putative extracellular domain (Wharton et al., 1985). Similarly, the nematode homeotic gene lin-12, required for normal cell fate switching during reproductive system development, consists of 11 EGF-like repeats (Greenwald, 1985). The drosophilia gene torpedo, which is involved in establishment of the embryonic dorsal–ventral axis, is a transmembrane protein with an extracellular domain and a tyrosine kinase domain homologous to those of the EGF receptor (Price et al., 1989). These analogies are based on sequence similarities of the genes, without direct biochemical evidence that the mechanisms of signal transduction by the homeotic gene products are similar to those utilized by EGF. Nonetheless, the homology shared between these morphogenically essential genes and EGF or its receptor implicate this growth factor family in developmental regulation.
Effects of Retinoids at the Cellular Level (Differentiation, Apoptosis, Autophagy, Cell Cycle Regulation, and Senescence)
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
Activation of RAR and PPAR by RA is crucial for induction of neuronal differentiation, and various target genes have been reported to be involved in this process (25,26). RA, through its effectors, directly regulates expression of subset of homeotic genes (Hox) Hoxa-1, Hoxb-2, and Wnt-1 (27). These master control genes specify the body plan and regulate the development and morphogenesis of higher organisms. In addition, RA also indirectly regulates achaete-scute family bHLH transcription factor 1 gene (ASCL1), Neurogenin 1 (NEUROG1), neuronal differentiation 1 (NeuroD1), N-cadherin/cadherin 2 (CDH2), and pre-B-cell leukemia transcription factors or PBX homeobox genes (Pbx) (7).
Regulation of Cell Functions
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
Homeotic genes may have a role in the regulation of hormone and growth factor secretion. The mammalian homeotic gene GHF1 is involved in the regulation of growth hormone gene expression in anterior pituitary somatotrophs.131 Transcription of the GHF1 gene is highly restricted and depends on positive autoregulation by the GHF1 protein as well as environmental influences acting through regulation of the intracellular levels of cAMP and the activity of the cAMP response element-binding (CREB) protein. Endogenous retinoids (vitamin A derivatives) may function as natural morphogens and may be involved in the regulation of homeotic gene expression. Little is known, however, about the regulatory effects of hormones and growth factors on homeotic gene expression. Some homeotic genes exhibit structural homology to the genes encoding growth factors such as EGF and TGF-α.132,133
MLLT10 promotes tumor migration, invasion, and metastasis in human colorectal cancer
Published in Scandinavian Journal of Gastroenterology, 2018
Xiaoqian Jing, Haoxuan Wu, Xi Cheng, Xianze Chen, Yaqi Zhang, Minmin Shi, Tao Zhang, Xiongjun Wang, Ren Zhao
Mixed lineage leukemia (MLL), a crucial controller of hematopoiesis, encodes a highly conserved transcription factor being a part of the Trithorax family of transcriptional activators [4]. MLL is also a regulator of homeotic genes (Hox genes) and is associated with the development of leukemia [5–8]. MLLT10, also known as AF10, is located at 10p12. As a recurrent MLL partner, AF10 participates in translocation with the clathrin-assembly lymphoid–myeloid (CALM) gene [9,10]. Recent studies have shown that the translocations t(10;11)(p12;q23) and t(10;11)(p12;q14), which result in MLL-AF10 and CALM-AF10 fusion proteins, are almost exclusively found in patients with acute myeloid or acute lymphoid leukemia [11,12]. Molecular analyses of MLL- and CALM-AF10 rearrangements demonstrate differences in the location of MLLT10 breakpoints [13].
Increased expression of TGF-β protein in the lesional skins of melasma patients following treatment with platelet-rich plasma
Published in Journal of Cosmetic and Laser Therapy, 2019
Eman R. M. Hofny, Mahmoud Rezk Abdelwahed Hussein, Alaa Ghazally, Asmaa M. Ahmed, Amira A. Abdel-Motaleb
In normal skin, TGF-β is expressed by the keratinocytes, fibroblasts, endothelial cells and some dermal mesenchymal and inflammatory cells (27–29). We found decreased expression values of TGF-β protein in both prelesional and lesional skin of the patients with melasma as compared to the health control skins. This decrease may be reasoned to sun exposure-related suppression of TGF-β production both at transcriptional (mRNA) and translational (protein) levels. The reduced TGF-β expression is associated with amelioration of its inhibitory effects on the cutaneous melanocytes, with subsequent enhancement of melanogenesis (melanin production), epidermal hyperpigmentation and the development of melasma. Our proposition is supported by several experimental observations. Exposure to UV irradiation is associated with suppression (15,30) or even cessation (22) of TGF-β expression at the transcriptional and protein levels both in the epidermal keratinocytes and in the fibroblasts. In the absence of UV radiation, TGF-β is released by the keratinocytes, which induces Smad signaling in melanocytes to repress paired-box homeotic gene (PAX3) and therefore block melanocyte differentiation, i.e., TGF-β negatively regulates melanocytes. TGF-β is the most important regulator of PAX-3 in adult melanocytes (15,22). The protein encoded by paired-box homeotic gene 3 is a key regulator of the microphthalmia-associated transcription factor (MITF) in the melanocyte lineage. PAX3 encodes a transcription factor crucial for melanocyte differentiation. Following UV irradiation, a Jnk/AP-1 pathway inhibits TGF-β, which together with a UV-induced p53 pathway stimulate the differentiation of the cutaneous melanocyte (15,22). Moreover, in vitro, TGF-β induces melanocyte immaturity by downregulating MITF. The latter is a transcriptional regulator of melanocyte differentiation, and its downstream melanogenic genes. In vivo, activation of TGF-β signaling contributes to the entry of the melanocyte stem cells in the quiescent noncycling state (31).