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Guanosine Triphosphate-Binding Proteins
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
The Ras subfamily includes the three mammalian Ras proteins (c-H-Ras, c-K-Ras, and N-Ras), as well as Rap (RaplA, RaplB, Rap2A, Rap2B) and Ral (RalA, RalB) proteins. The Rho protein subfamily includes the Rho proteins (RhoA, RhoB, RhoC), as well as Rac proteins (Rac 1, Rac2) and other members. The Rab subfamily includes the Rab proteins (RablA, RablB, Rab2, Rab3A, Rab3B, Rab3C, Rab4A, Rab4B, and Rab5 to Rabl 1), the Ypt proteins (Yptl, Ypt2, Ypt3), and the Sas, Sec, and Ara proteins. The members of the Ras subfamily of proteins are located, with few exceptions, on the cytoplasmic face of the plasma membrane in mammalian cells. The members of the Rho subfamily are associated mainly with the cytoplasm and the Golgi complex and are involved in actin organization and control of cell shape, probably by interacting with the cytoskeleton and intracellular membranes. The Rab-related proteins are involved in vesicular traffic and are associated with a variety of cellular compartments. Expression of the members of the Ras protein superfamily in mammalian cells is ubiquitous, although Rab3 A is found only in cells of neural origin.
PROTACs for BRDs proteins in cancer therapy: a review
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Chao Wang, Yujing Zhang, Shanbo Yang, Wujun Chen, Dongming Xing
Derived from the potent BRD4 inhibitor JQ-1, the first von Hippel-Lindau (VHL)-based PROTAC targeting BRD4 named PROTAC 17 (Figure 8) was reported by Zengerle et al. in 201550. PROTAC 17-induced protein degradation was dependent on binding to VHL E3 ubiquitin ligase. PROTAC 17 showed preferential degradation of BRD4 over BRD2 and BRD3 at low concentrations (When the concentration of PROTAC 17 was 1 μM, more than 90% of BRD4 protein was removed.). Selective depletion of BRD4 with PROTAC 17 produced a different pharmacological response compared to inhibition of the whole BET protein subfamily with JQ-1. Preferential direct interaction or reduced steric constraint between VHL and BRD4 might occur as a result of PROTAC binding, triggering a more productive formation of the VHL-PROTAC 17-BRD4 ternary complex compared to BRD2/3. They concluded that efficient and selective degradation of BRD4 with the PROTAC approach provided an unprecedented opportunity to study the downstream physiological and pathological consequences of BRD4 regulation.
Clinical and genetic characteristics of nevus of Ota with choroidal melanoma in Chinese
Published in Ophthalmic Genetics, 2019
The exact etiology of nevus of Ota is still unknown. Although familial cases are rare, there may be an underlying genetic predisposition (13,14). Dr. Konstantinov found that GNAQ and BAP1 mutations in patients with nevus of Ota confer a greater risk for malignant melanoma and metastatic progression (7,15,16). In our series, we found two suspicious gene mutations involving FAM111B and DSC2 that might contribute to the etiology of the disease. The missense variants c.304T>C (p. Tyr102His) and c.2608G>C (p. Gly870Arg) were discovered in FAM111B and DSC2, respectively, according to our results. FAM111B is located in 11q12.1 and encodes a protein with a trypsin-like cysteine/serine peptidase domain in the C-terminus. Mutations in FAM111B are associated with hereditary fibrosing poikiloderma (HFP) (5). There is no current evidence to prove that FAM111B is associated with nevus of Ota. However, individuals with these gene mutations could display mottled pigmentation, which might indicate some relationship between FAM111B and nevus of Ota. DSC2, which is located in 18q12.1, encodes a member of the desmocollin protein subfamily. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia, reduced protein expression in several types of cancer, and tumor progression in esophageal cell carcinoma, gastric cancer, colon cancer, etc (6). No previous findings indicate whether DSC2 plays a role in nevus of Ota. DSC2 may be a new breakthrough for the disease. Further studies should identify the relationship between DSC2 and nevus of Ota.
Prognostic biomarkers for cholangiocarcinoma and their clinical implications
Published in Expert Review of Anticancer Therapy, 2018
Charupong Saengboonmee, Kanlayanee Sawanyawisuth, Yaovalux Chamgramol, Sopit Wongkham
LIM and SH3 protein (LASP) 1, a member of a LIM protein subfamily characterized by a LIM motif and a domain of Src homology region 3, functions as an actin-binding protein and cytoskeletal organization. The association of LASP1 with progression and metastatic dissemination was reported in medulloblastoma [40]. In CCA, LASP1 was associated with proliferation, migration, invasion and tumorigenesis of CCA in vivo [41]. High expression of LASP1 in CCA tissues was positively correlated with the larger tumor, poor histological differentiation, lymph node metastasis, an advanced TNM stage, and shorter OS of patients. Moreover, suppression of LASP1 increased apoptosis and suppressed proliferation, migration, and invasion of CCA cell lines. LASP1 is, thus, a promising prognostic factor and a candidate for being a therapeutic target.