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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
Genes activated by RA are members of different signaling pathways including TGF-β pathway (genes left-right determination factor 2 [LEFTY2], BMP and activin membrane bound inhibitor [BAMBI], Follistatin [FST]), homeodomain pathway (genes HoxD1, MEIS1, MEIS2), gastrulation brain homeobox 2 (GBX2), insulin growth factor (IGF) pathway (genes IGFBP3, IGFBP6, CTGF), Notch pathway (genes manic fringe [MFNG] and metallopeptidase domain 11 [ADAM11]), Hedgehog pathway (gene Patched [PTCH]) and Wnt pathway (genes FRAT2 and secreted frizzled-related protein 1 [SFRP1]) (19). In addition, transcription factors from Sry-related HMG box (SOX) gene family are upregulated during the RA induced neural differentiation, such as SOX3, one of the earliest neural markers (28). It has been postulated that cumulative regulation of SOX target genes during neurogenesis is the result of a fine balance between gene expression control regulated by members of SOXB1 (SOX1, SOX2, SOX3) and SOXB2 (SOX14 and SOX21) gene subfamilies (29–31). The increase in SOXB2 protein levels activates proneural proteins, which subsequently interfere with SOXB1 function, leading to differentiation of a neural progenitor towards neuronal phenotype (29). Members of SOXB subfamily are directly (32–34) and indirectly (35–37) regulated by RA and RA effector signaling. SOXB protein expression changes during the course of differentiation (20), which makes them a group of genes that participate in RA mediated proliferation-differentiation switches.
The significance of the neuregulin-1/ErbB signaling pathway and its effect on Sox10 expression in the development of terminally differentiated Schwann cells in vitro
Published in International Journal of Neuroscience, 2021
Xizhong Yang, Cuijie Ji, Xinyue Liu, Chaoqun Zheng, Yanxin Zhang, Ruowu Shen, Zangong Zhou
Neuregulin-1 (NRG-1) is a member of the family of regulatory proteins that contain the EGF (epidermal growth factor)-like domain. It is a type of transmembrane protein that regulates the growth and development of glial cells and neurons [8]. The functional receptor of NRG is the ErbB receptor, which includes ErbB2/HER2, ErbB3/HER3, and ErbB4/HER4. ErbB is a member of the EGF receptor family of transmembrane tyrosine kinases. Both ErbB2 and ErbB3 receptors are required in the development of SCs, but these two receptors have different effects; ErbB3 can bind with extracellular ligands with high affinity even though it is inactive, while ErbB2 tyrosine kinase activity can activate downstream signaling [9]. Sox10 belongs to the Sox family, members of which contain a DNA binding domain that is similar to the HMG (high mobility group) domain of the SRY transcription factor family [10]. The structure of Sox10 is highly conserved, especially the structure of its functional domains, such as the N-terminal to C-terminal dimerization domain, the HMG domain, and the protein interaction (K2) domain [11]. The Sox gene family is involved in stem cell maintenance, cell differentiation and tissue formation. Sox10 plays an important role in the formation of the neural crest and peripheral nervous system, the maturation and terminal differentiation of SCs, and the differentiation of melanocytes. Sox10 and Oct6 have synergistic effects on the differentiation and development of SCs [12]. In addition, in the central nervous system and the peripheral nervous system, Sox10 is highly expressed in neural crest cells and glial cells.
Augmented angiogenic transcription factor, SOX18, is associated with asthma exacerbation
Published in Journal of Asthma, 2021
Jisu Hong, Pureun-Haneul Lee, Yun-Gi Lee, George D. Leikauf, An-Soo Jang
The SOX gene family members contain high mobility group (HMG) box DNA binding regions and are related to the mammalian sex determining gene region of the Y (SRY). The gene SRY (sex determining region of the Y), located at the distal region of the short arm of the Y chromosome, is necessary for male sex determination in mammals. SOX genes play key roles during animal development (9,39–41), showing diverse and dynamic patterns of expression throughout embryogenesis and in a variety of adult tissue types. Mouse Sox 1, 2, and 3 are expressed at the highest level in the developing nervous system and human SOX 1–4, 10, 11, 14 and 22 genes are expressed in developing brain (42–47). Base on the sequence of its HMG box, human SOX18 along with SOX7 and SOX17, are classified as a member of the F subfamily (48,49).
Molecular diagnostics of disorders of sexual development: an Indian survey and systems biology perspective
Published in Systems Biology in Reproductive Medicine, 2019
MR Nagaraja, Satya Prakash Gubbala, C. R. Wilma Delphine Silvia, Ramars Amanchy
Human sex-determining region Y (SRY) protein (204 amino acids) coded by an intronless gene, SRY (a member of SOX gene family, cytogenetic location-Y chromosome p11.2), consists of three parts, i.e., N-terminus part (1–56 codons), high mobility group (HMG) domain (57 ± 136, 80 codons), and C-terminus part (137 ± 204, 68 codons). This DNA-binding protein is responsible for the initiation of male sex determination. In XY fetus, inactivating SRY mutation fails to activate its target genes, in turn bipotential gonad remains undifferentiated leading to complete GD (CGD) (<20% cases) evidenced by streak gonads, presence of uterine remnants (no AMH production), and female external genitalia (no androgen synthesis). These cases usually present at adolescence due to delayed pubarche and primary amenorrhea or may at later adulthood because of gonadal tumors (unilateral or bilateral dysgerminoma) or other tumors (gonadoblastoma, teratoma, or embryonal carcinoma).