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Adipose tissue is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells such as adipose tissue macrophages. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body.
A ubiquitin ligase is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. In simple and more general terms, the ligase enables movement of ubiquitin from a ubiquitin carrier to another thing by some mechanism. The ubiquitin, once it reaches its destination, ends up being attached by an isopeptide bond to a lysine residue, which is part of the target protein. E3 ligases interact with both the target protein and the E2 enzyme, and so impart substrate specificity to the E2. Commonly, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin, targeting the substrate for destruction by the proteasome. However, many other types of linkages are possible and alter a protein's activity, interactions, or localization. Ubiquitination by E3 ligases regulates diverse areas such as cell trafficking, DNA repair, and signaling and is of profound importance in cell biology. E3 ligases are also key players in cell cycle control, mediating the degradation of cyclins, as well as cyclin dependent kinase inhibitor proteins. The human genome encodes over 600 putative E3 ligases, allowing for tremendous diversity in substrates.
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. In cell culture, adipocyte progenitors can also form osteoblasts, myocytes and other cell types.
Ubiquitin-protein ligase E3A (UBE3A) also known as E6AP ubiquitin-protein ligase (E6AP) is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells.
CCAAT-enhancer-binding proteins is a family of transcription factors composed of six members, named from C/EBPα to C/EBPζ. They promote the expression of certain genes through interaction with their promoters. Once bound to DNA, C/EBPs can recruit so-called co-activators that in turn can open up chromatin structure or recruit basal transcription factors.
Niemann-Pick disease, type C1 (NPC1) is a membrane protein that mediates intracellular cholesterol trafficking in mammals. In humans the protein is encoded by the NPC1 gene.
E3 ubiquitin-protein ligase NEDD4, also known as neural precursor cell expressed developmentally down-regulated protein 4 is an enzyme that is, in humans, encoded by the NEDD4 gene.
Cullin-4A is a protein that in humans is encoded by the CUL4A gene. CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates numerous key processes such as DNA repair, chromatin remodeling, spermatogenesis, haematopoiesis and the mitotic cell cycle. As a result, CUL4A has been implicated in several cancers and the pathogenesis of certain viruses including HIV. A component of a CUL4A complex, Cereblon, was discovered to be a major target of the teratogenic agent thalidomide.
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is a signal transduction enzyme that in humans is encoded by the autosomal MAP3K1 gene.
DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene.
Cullin-2 is a protein that in humans is encoded by the CUL2 gene.
Cullin-4B is a protein that in humans is encoded by the CUL4B gene which is located on the X chromosome. CUL4B has high sequence similarity with CUL4A, with which it shares certain E3 ubiquitin ligase functions. CUL4B is largely expressed in the nucleus and regulates several key functions including: cell cycle progression, chromatin remodeling and neurological and placental development in mice. In humans, CUL4B has been implicated in X-linked intellectual disability and is frequently mutated in pancreatic adenocarcinomas and a small percentage of various lung cancers. Viruses such as HIV can also co-opt CUL4B-based complexes to promote viral pathogenesis. CUL4B complexes containing Cereblon are also targeted by the teratogenic drug thalidomide.
Cullin 3 is a protein that in humans is encoded by the CUL3 gene.
GTP-binding protein Rit1 is a protein that in humans is encoded by the RIT1 gene.
Chemerin, also known as retinoic acid receptor responder protein 2 (RARRES2), tazarotene-induced gene 2 protein (TIG2), or RAR-responsive protein TIG2 is a protein that in humans is encoded by the RARRES2 gene.
Adipogenesis is the formation of adipocytes from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as lipoblasts or preadipocytes which lose the potential to differentiate to other types of cells such as chondrocytes, myocytes, and osteoblasts. Terminal differentiation is that preadipocytes differentiate into mature adipocytes. Adipocytes can arise either from preadipocytes resident in adipose tissue, or from bone-marrow derived progenitor cells that migrate to adipose tissue.
Cereblon is a protein that in humans is encoded by the CRBN gene. The gene that encodes the cereblon protein is found on the human chromosome 3, on the short arm at position p26.3 from base pair 3,190,676 to base pair 3,221,394. CRBN orthologs are highly conserved from plants to humans.
Krüppel-like factor 15 is a protein that in humans is encoded by the KLF15 gene in the Krüppel-like factor family. Its former designation KKLF stands for kidney-enriched Krüppel-like factor.
Motile sperm domain containing 2 is a protein that in humans is encoded by the MOSPD2 gene. It is an endoplasmic reticulum–resident protein involved in membrane contact site formation. Its domain homologous to Major Sperm Protein is very similar to VAPA/VAPB, so it has been described as the third human member of the VAP protein family.
Asprosin is a protein hormone produced by mammals in tissues that stimulates the liver to release glucose into the blood stream. Asprosin is encoded by the gene FBN1 as part of the protein profibrillin and is released from the C-terminus of the latter by specific proteolysis. In the liver, asprosin activates rapid glucose release via a cyclic adenosine monophosphate (cAMP)-dependent pathway.
References
- ↑ Suh JM, Zeve D, McKay R, Seo J, Salo Z, Li R, et al. (September 2007). "Adipose is a conserved dosage-sensitive antiobesity gene". Cell Metabolism. 6 (3): 195–207. doi:10.1016/j.cmet.2007.08.001. PMC 2587167 . PMID 17767906.
- ↑ "ScienceDaily: 'Skinny Gene' Exists" . Retrieved 2007-09-05.
- ↑ Lai CQ, Parnell LD, Arnett DK, García-Bailo B, Tsai MY, Kabagambe EK, et al. (March 2009). "WDTC1, the ortholog of Drosophila adipose gene, associates with human obesity, modulated by MUFA intake". Obesity. 17 (3): 593–600. doi:10.1038/oby.2008.561. PMC 2874970 . PMID 19238144.
- ↑ Ducos E, Vergès V, Dugé de Bernonville T, Blanc N, Giglioli-Guivarc'h N, Dutilleul C (September 2017). "Remarkable Evolutionary Conservation of Antiobesity ADIPOSE/WDTC1 Homologs in Animals and Plants". Genetics. 207 (1): 153–162. doi: 10.1534/genetics.116.198382 . PMC 5586369 . PMID 28663238.
- ↑ Groh BS, Yan F, Smith MD, Yu Y, Chen X, Xiong Y (May 2016). "The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase". EMBO Reports. 17 (5): 638–47. doi:10.15252/embr.201540500. PMC 5341520 . PMID 27113764.
- ↑ Groh BS, Yan F, Smith MD, Yu Y, Chen X, Xiong Y (May 2016). "The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase". EMBO Reports. 17 (5): 638–47. doi:10.15252/embr.201540500. PMC 5341520 . PMID 27113764.