Reticular hyperpigmentation
Dimitris Rigopoulos, Alexander C. Katoulis in Hyperpigmentation, 2017
RAK is a rare genodermatosis that is inherited in an autosomal dominant manner, and is caused by mutations on the ADAM10 gene, mapped on chromosome 15q21.3.77 The exact incidence of the condition is unknown. In general, cases have been reported in association with most ethnic backgrounds; however, the vast majority of patients are of Japanese origin.77 A number of authors have suggested that RAK should be considered a variant of DDD; however, this remains highly controversial, as the two disorders are caused by different gene mutations and exhibit distinct phenotypes. In RAK, loss-of-function mutations in ADAM10 are commonly observed.77 The ADAMs are considered a new gene family that belong to the zinc protease superfamily.78,79 More specifically, ADAM10 has been shown to play a role in the ectodomain shedding of various substrates in the skin, such as the L1 cell adhesion molecule (L1-CAM), CD44, E-cadherin, N-cadherin, IL-6R, and CD30.80 At this point, the exact pathogenetic mechanism of RAK is not well understood, but ADAM10 haploinsufficiency was recently reported to cause freckle-like macules in specific murine models.81
The Importance of Sperm Surface Markers in Reproductive Success: Sperm Hyaluronan Binding
Nicolás Garrido, Rocio Rivera in A Practical Guide to Sperm Analysis, 2017
The quality of the epididymal maturation strongly influences sperm fertilizing capacity. Thus, sperm protein markers during maturation steps are among the most promising tools. However, only few sperm surface maturation proteins, such as fertilin, have been described with a role in fertility in large mammals because most studies were performed on rodents. Fertilin, a heterodimer complex composed of two integral membrane glycoproteins named alpha-fertilin (ADAM-1) and beta-fertilin (ADAM-2), as well as several other ADAMs, has been reported to be involved in sperm–oocyte recognition and in membrane fusion.22,23 Fertilin binds to integrin α6 β1 leading to sperm–egg binding and membrane fusion.24 The fertility of male mice lacking alpha-fertilin or beta-fertilin is substantially reduced due to sperm inability to migrate through the oviduct and to bind to the zona pellucida and to the oocyte plasma membrane.22,25
Bacteriology of Ophthalmic Infections
K. Balamurugan, U. Prithika in Pocket Guide to Bacterial Infections, 2019
The alpha-toxin binds to the protease receptor ADAM 10; thereby it can form pores on the cell membrane, allowing small molecules to pass through. The binding of alpha-toxin with the immune cells such as neutrophils, monocytes, T-cells, and platelets allow calcium ions to pass through the pores and thus causing cellular dysregulation. It can also cleave the E-cadherin molecules, which are associated with the attachment of cells. Thus, the alpha-toxin binding to the corneal epithelium will eventually disrupt the epithelial layer and initiate the corneal ulceration. In endophthalmitis, the alpha-toxin can cause inflammation in the retina, which can terminate in loss of retinal function (Berube and Juliance, 2013; Kumar and Kumar, 2015).
Local delivery of interleukin 7 with an oncolytic adenovirus activates tumor-infiltrating lymphocytes and causes tumor regression
Published in OncoImmunology, 2022
Tatiana V. Kudling, James H.A. Clubb, Dafne C.A. Quixabeira, Joao M. Santos, Riikka Havunen, Alexander Kononov, Camilla Heiniö, Victor Cervera-Carrascon, Santeri Pakola, Saru Basnet, Susanna Grönberg-Vähä-Koskela, Victor Arias, Ivan Gladwyn-Ng, Katri Aro, Leif Bäck, Jari Räsänen, Ilkka Ilonen, Kristian Borenius, Mikko Räsänen, Otto Hemminki, Antti Rannikko, Anna Kanerva, Johanna Tapper, Akseli Hemminki
The analysis of the tumor microenvironment showed a clear shift toward proinflammatory signaling in ex vivo patient samples infected with Ad5/3-E2F-d24-hIL7, particularly, increased IFNg production, which, in turn, stimulates expression of Ccl5, Cxcl9 and Cxcl10 – key chemokines involved in the recruitment of T cells and NK cells. Indeed, we observed higher number of CD4+ and CD8+ migrated cells when used supernatants obtained after infection with IL7 armed virus. Transcriptomic analysis showed upregulation of several migration-related genes in CD4+ cells – CCR5, DPP4, ITGA4, MYO1G. Interestingly, we observed significant upregulation of ADAM19 gene in both CD4+ and CD8 + T cell, however, the role of this particular protein in immune cells is still unclear. ADAM proteins are membrane disintegrins and metalloproteinases, which convert nearby membrane-anchored cytokine precursors, cytokine receptors, Notch receptors, phagocytic receptors or cell adhesion molecules into soluble bioactive mediators.31 In T cells, ADAMs can be involved in cell development and activation via cleavage of negative regulatory proteins, such as LAG3,32 and regulate cell migration not only due to the proteolytic activity of ADAMs on the T cells themselves, but also due to the protease activity on the tissue cells serving as substrate of cell migration.33 Nevertheless, additional experiments are needed to understand the role of ADAM19 in T cells activation and migration upon Ad5/3-E2F-d24-hIL7 infection.
Transmembrane protein ADAM29 facilitates cell proliferation, invasion and migration in clear cell renal cell carcinoma
Published in Journal of Chemotherapy, 2020
Shun-Lai Li, Ting-Qi Jiang, Qing-Wei Cao, Shan-Mei Liu
A disintegrin and metalloprotease (ADAM) family, also known as metalloproteinolytic depolymerization, is a type І transmembrane protein.9 It has a zinc binding domain similar to that of matrix metalloproteinases (MMPs) and a functional binding domain similar to that of the metalloprotease-disintegrin-cysteinerich (MDC) family, which plays a role in proteolytic processing of cell surface molecules and in cell adhesion.10,11 The involvement of ADAMs in regulation of cell-cell adhesion and cell-matrix interactions suggests that they not only play a potential effect in normal physiological processes, but also provide a basis for considering the participation in tumour biology and their ability to invade and metastasize.12 Previous reports have demonstrated that multiple members of ADAM family, including ADAM29, are abnormally expressed in a variety of cancers, which may be closely connected with the development of tumours.13–16 Currently, in RCC, several ADAMs (8, 9, 17, 19, and 28) have already been shown upregulated on transcript level, with ADAM8 and ADAM9 being correlated with poor survival and distant metastasis.17,18 But, the role of ADAM29 in ccRCC remains unclear.
Recent developments and strategies for the discovery of TACE inhibitors
Published in Expert Opinion on Drug Discovery, 2020
Prashant R. Murumkar, Rahul B. Ghuge, Monica Chauhan, Rahul R. Barot, Sharmishtha Sorathiya, Kailash M. Choudhary, Karan D. Joshi, Mange Ram Yadav
Activities of ADAMs are mainly governed by the prodomain component. ADAMs consist of a long sequence of around 750 amino acids. In humans, about 22 ADAM genes have been identified till date. Various transmembrane proteins are cleaved by ADAMs at the location of plasma membrane through an ectodomain shedding process [3]. Within this ADAMs family, ADAM17, a zinc metalloproteinase also known as TNF-α Converting Enzyme (TACE) (Figure 1(b)), is observed to be holding a central place in different pathophysiological conditions. TACE plays an important role in the release of TNF-α which is involved in the processing of cell adhesion proteins like L-selectin and ICAM1, cytokine receptors like IL6 R and TNFR, and ligands of EGF receptors. TACE converts 26 kDa, pro-TNF-α into 17 kDa soluble mature TNF-α protein through proteolytic process and releases it into blood circulation [3].
Related Knowledge Centers
- Adamts
- Animal
- Protein Domain
- Transmembrane Protein
- Metalloendopeptidase
- Protein–Protein Interaction
- Sheddase
- Her2
- Proteases In Angiogenesis