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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).
William Bateson (1861–1926)
Published in Krishna Dronamraju, A Century of Geneticists, 2018
In common with Darwin, he felt that quantitative characters could not easily be “perfected” by the selective force of evolution, because of the perceived problem of the “swamping effect of intercrossing,” but proposed that discontinuously varying characters could. Among other interesting observations he noted were variations in which an expected body part has been replaced by another (which he called “homeotic”). The animal variations he studied included bees with legs instead of antennae; crayfish with extra oviducts; and in humans, polydactyly, extra ribs, and males with extra nipples.
Regulation of Cell Functions
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
Homeobox-containing genes (homeotic genes or Hox genes) have an essential role in the regulation of developmental processes by morphogens and growth factors.114-120 The homeobox is a sequence of 183 bp that was originally discovered in genes associated with homeotic mutations (i.e., changes in segment identity leading to transformation of one body structure into another) in the fruit fly, Drosophila melanogaster. Homeotic genes are activated in a defined spatial and temporal sequence during the process of developmental segmentation of the insect. Homeobox-containing genes are present in vertebrates, including humans.121 No less than 30 homeobox-containing genes have been identified in the human genome.122-124 Human homeotic genes are distributed in four main clusters, termed HOX1 to HOX4, which reside on different human chromosomes: HOX1 includes 8 homeoboxes in 90 kb of DNA on chromosome 7, HOX1 includes 9 homeoboxes in 180 kb of DNA on chromosome 17, HOX3 contains at least 7 homeoboxes in 160 kb of DNA on chromosome 12, and HOX4 includes 6 homeoboxes in 70 kb of DNA on chromosome 2. The homeobox encodes a 61-amino acid helix-turn-helix (HTH) protein structure that binds DNA with sequence specificity. Homeobox proteins may function as transcription factors involved in the regulation of gene expression; however, the identity of target genes regulated by homeobox proteins is almost unknown.
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
The therapeutic efficacy of PRP is reasoned to its abundant contents of growth factors including TGF-β. The latter is a multifunctional natural polypeptide with three major isoforms namely TGF-β1, β2, and β3 that signal through type I and type II TGF-β receptors (13).TGF-β is released as an inactive form from the platelets α-granules of PRP and then become activated by the proteolytic cleavage. In the skin, TGF-β family regulates several cell functions including cell proliferation, differentiation, and melanogenesis (14). Several observations support a role for TGF-β in regulating melanogenesis. In the spontaneously immortalized mouse melanocyte cell line, TGF-β1 significantly repressed melanin synthesis (melanogenesis) through several mechanisms such as delayed extracellular signal-regulated kinase activation (6).TGF-β1 can reduce the activity of tyrosinase, tyrosinase-related proteins and the promoter of the microphthalmia transcription factor (MITF). TGF-β can delay the activation of extracellular signal-regulated kinase. Also, TGF-β can repress the expression of paired-box homeotic gene (PAX), which regulate UV-induced melanogenesis (15). Recent studies have indicated clinical improvement in skin of melasma patients following PRP injection, possibly due to its abundant contents of growth factors such as TGF-β. These studies also proposed the use of PRP as a new therapeutic modality in melasma. However, to date the underlying mechanisms of the clinical improvement is unknown (8,9). Whether PRP injection would be associated with alterations in the levels of TGF-β is not yet elucidated.
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].
Shining a light on cell signaling in leukemia through proteomics: relevance for the clinic
Published in Expert Review of Proteomics, 2018
Fieke W. Hoff, Chenyue W. Hu, Amina A. Qutub, Eveline S. J. M. de Bont, Terzah M. Horton, Steven M. Kornblau
Our group has previously performed RPPA on 511 AML patients and, when compared to normal CD34+ cells, identified Forkhead O Transcription Factor 3A (FOXO3A), Bromodomain Containing 4 (BRD4), Absent, Small, Or Homeotic Discs-like Protein (ASH2L), Tripartite Motif Containing 62 (TRIM62), and Friend Leukemia Virus Integration 1 (FLI1) as prognostic factors that were significantly associated with OS. FOXO3A was found to be expressed within the range of the healthy control samples but was higher at relapse compared to diagnosis. Also, higher FOXO3A phosphorylation, or a higher ratio between phosphorylated and total FOXO3A, were associated with primary chemoresistance and a shorter relapse free survival and OS [28]. Higher BRD4 levels were found to predict shorter OS (ASH 2017 #3794), lower ASH2L was associated with increased OS [29] and loss of TRIM62 related to a shorter CR duration and OS [30]. For FLI1, both increased and decreased expression was associated with a shorter remission duration and OS [31]. Ruvolo et al. found that phosphorylation of Glycogen Synthase Kinase 3 α/β (GSKα/β) correlated with activation of AKT and that GSK activation was prognostic for poor OS [32]. They also found that the protein phosphatase 2A (PP2A) regulatory subunit B55α was lower expressed in AML compared to normal CD34+ cells, and that low levels of PP2A B55α were associated with a shorter CR duration [33]. Within adult ALL, cathepsin G protein expression measured by RPPA was also a poor prognostic marker [34].