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Topic Review
Biography
Topic Review
SUMOylation
SUMOylation is a dynamic and essential Post-Translation Modification (PTM) consisting on the conjugation of Small Ubiquitin-like Modifiers (SUMOs) to an acceptor lysine of a substrate protein. SUMOylation predominantly regulates nuclear processes and its dysregulation is associated to diseases including cancer. SUMOs share a similar three-dimensional structure with other Ubiquitin-Like Modifiers (UBLs). However, SUMOs differ due to their flexible N-terminus, which also contains the site for SUMO chain formation. All eukaryotes express at least one SUMO paralogue. Five SUMO family members have been identified in humans (SUMO1, SUMO2, SUMO3, SUMO4, and SUMO5. However, SUMO1, SUMO2, and SUMO3 are the main family members where they are commonly classified as SUMO1 and SUMO2/3 because of the high similarity between mature SUMO2 and SUMO3. All SUMO paralogues are similar in structure but differ in expression levels. SUMO2 is the most abundant family member in mammalian cells. Studies in mice show that the knockout of SUMO2 is embryonic lethal, while SUMO1 and SUMO3 knockout mice were associated to mild phenotypes, possibly because SUMO2 might compensate the loss of either SUMO1 or SUMO3. Similarly to ubiquitination, SUMO is conjugated in a in a 3-step enzymatic cascade that involves a dimeric E1 activating enzyme (SAE1 and SAE2), an E2 conjugating enzyme (Ubc9), and several SUMO E3 enzymes.
585
28 Mar 2022
Topic Review
Exosomes and Diabetes
Diabetes is part of a group of metabolic disorders characterized by long-term high blood glucose levels due to either inadequate production of insulin (type 1) or poor response of the recipient cell to insulin (type 2). Organ dysfunctions are the main causes of morbidity and mortality due to high glucose levels. Exosomes are part of a newly emerged research area and have attracted a great deal of attention for their capacity to regulate communications between cells. In conditions of diabetes, exosomes play important roles in the pathological processes in both T1DM and T2DM, such as connecting the immune cell response to pancreatic tissue injury, as well as adipocyte stimulation to insulin resistance of skeletal muscle or liver. Furthermore, in recent years, nucleic acids containing exosomes—especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs)—have been shown to mainly regulate communications between organs in pathological processes of diabetes, including influencing metabolic signals and insulin signals in target tissues, affecting cell viability, and modulating inflammatory pancreatic cells. Moreover, exosome miRNAs show promise in their use as biomarkers or in treatments for diabetes and diabetic complications.
989
25 Mar 2022
Topic Review
Vav1 Promotes B-Cell Lymphoma Development
Vav1 is normally and exclusively expressed in the hematopoietic system where it functions as a specific GDP/GTP nucleotide exchange factor (GEF), firmly regulated by tyrosine phosphorylation. Mutations and overexpression of Vav1 in hematopoietic malignancies, and in human cancers of various histologic origins, are well documented. The research results suggest that overexpressing Vav1 in epithelial tissues induced chronic inflammatory reactions eventually leading to B-cell lymphomas development. The development of the lymphomas was accompanied by an increase in ERK phosphorylation, elevation of CSF- in the epithelial tissue, and an increase in CSF1-R expression in the lymphomas. These findings provide a novel mechanism by which Vav1 contributes to tumor propagation.
618
25 Mar 2022
Topic Review
Deciphering Tumour Heterogeneity
Decoding tumour heterogeneity is a major clinical challenge, considering that it immensely contributes to cancer progression, treatment failure and emergence of drug resistance. Emerging technical and sampling strategies have been developed in order to deeply characterise tumour complexity and clonal architecture, including single-cell profiling, multi-region sampling, representative sampling and longitudinal analysis of liquid biopsy samples.
668
25 Mar 2022
Topic Review
STxB in Mucosal Vaccination
One mucosal vaccine candidate is the B-subunit of Shiga toxin, STxB. STxB is a non-toxic protein that binds to a glycosylated lipid, termed globotriaosylceramide (Gb3), which is preferentially expressed by dendritic cells.
525
25 Mar 2022
Topic Review
Primary Cilia in Acquired Heart Disease
Primary cilia are non-motile plasma membrane extrusions that display a variety of receptors and mechanosensors. Loss of function results in ciliopathies, which have been strongly linked with congenital heart disease, as well as abnormal development and function of most organ systems.
713
24 Mar 2022
Topic Review
Cell Signaling Pathways and Radioresistance of Cancer Cells
Radiation eradicates cancer cells mainly by causing DNA damage. However, radiation also concomitantly activates multiple prosurvival signaling pathways, which include those mediated by ATM, ATR, AKT, ERK, and NF-κB that promote DNA damage checkpoint activation/DNA repair, autophagy induction, and/or inhibition of apoptosis. Furthermore, emerging data support the role of YAP signaling in promoting the intrinsic radioresistance of cancer cells, which occurs through its activation of the transcription of many essential genes that support cell survival, DNA repair, proliferation, and the stemness of cancer stem cells. Together, these signaling pathways protect cancer cells by reducing the magnitude of radiation-induced cytotoxicity and promoting radioresistance.
664
24 Mar 2022
Topic Review
CircRNA Regulation of Skeletal Muscle Growth and Development
Circular RNA (circRNA) is a novel class of non-coding RNA generated by pre-mRNA back splicing, which is characterized by a closed-loop structure. The skeletal muscle is the largest organ in animals, which constitutes 30~–50% of the body mass. Skeletal muscle plays an important role in locomotion and metabolism. Therefore, proper muscle growth and homeostasis are the critical determinants of human motor performance. Recent studies showed that circRNAs are abundant in skeletal muscle tissue, and their expression levels are regulated during muscle development and aging.
446
23 Mar 2022
Topic Review
Ultraviolet Protection in the Cornea
Ultraviolet (UV) irradiation induces DNA lesions in all directly exposed tissues. In the human body, two tissues are chronically exposed to UV: the skin and the cornea. The most frequent UV-induced DNA lesions are cyclobutane pyrimidine dimers (CPDs) that can lead to apoptosis or induce tumorigenesis. Lacking the protective pigmentation of the skin, the transparent cornea is particularly dependent on nucleotide excision repair (NER) to remove UV-induced DNA lesions. The DNA damage response also triggers intracellular autophagy mechanisms to remove damaged material in the cornea. Therapeutic solutions involving xenogenic DNA-repair enzymes such as T4 endonuclease V or photolyases exist and are widely distributed for dermatological use.
583
23 Mar 2022
Topic Review
Circadian Regulation of Retinal Pigment Epithelium Function
The retinal pigment epithelium (RPE) is a single layer of cells located between the choriocapillaris vessels and the light-sensitive photoreceptors in the outer retina. The RPE performs physiological processes necessary for the maintenance and support of photoreceptors and visual function. Among the many functions performed by the RPE, the timing of the peak in phagocytic activity by the RPE of the photoreceptor outer segments that occurs 1–2 h. after the onset of light has captured the interest of many investigators and has thus been intensively studied. Several studies have shown that this burst in phagocytic activity by the RPE is under circadian control and is present in nocturnal and diurnal species and rod and cone photoreceptors. Previous investigations have demonstrated that a functional circadian clock exists within multiple retinal cell types and RPE cells. However, the anatomical location of the circadian controlling this activity is not clear. Experimental evidence indicates that the circadian clock, melatonin, dopamine, and integrin signaling play a key role in controlling this rhythm.
413
21 Mar 2022
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