The ubiquitin-proteasome pathway (UPP) is involved in regulating several biological functions, including cell cycle control, apoptosis, DNA damage response, and apoptosis. It is widely known for its role in degrading abnormal protein substrates and maintaining physiological body functions via ubiquitinating enzymes (E1, E2, E3) and the proteasome. Therefore, aberrant expression in these enzymes results in an altered biological process, including transduction signaling for cell death and survival, resulting in cancer. In this review, an overview of profuse enzymes involved as a pro-oncogenic or progressive growth factor in tumors with their downstream signaling pathways has been discussed. A systematic literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out to understand the nature of the extensive work done on modulation of ubiquitin-proteasome pathways in oncogenic signaling. Various in vitro, in vivo studies demonstrating the involvement of ubiquitin-proteasome systems in varied types of cancers and the downstream signaling pathways involved are also discussed in the current review. Several inhibitors of E1, E2, E3, deubiquitinase enzymes and proteasome have been applied for treating cancer. Some of these drugs have exhibited successful outcomes in in vivo studies on different cancer types, so clinical trials are going on for these inhibitors. This review mainly focuses on certain ubiquitin-proteasome enzymes involved in developing cancers and certain enzymes that can be targeted to treat cancer.
The
deposition of amyloid-β (Aβ) plaques and tau-based
neurofibrillary tangles is a neuropathological feature of Alzheimer’s
disease (AD). While studies have shown that the Aβ and tau interaction
results in elevated AD pathology, the molecular linkage and mechanism
of interaction of Aβ and tau are unclear. A recent study demonstrated
the direct interaction between the Aβ core and specific regions
of tau that facilitates pathological cross-seeding via a shared epitope.
The data suggest that targeting the common epitope could be a more
effective treatment strategy rather than targeting only Aβ or
only tau. The findings have an important clinical significance for
AD and related tauopathies.
Fascioliasis, a neglected foodborne disease caused by liver flukes
(genus Fasciola), affects more than 200 million people
worldwide. Despite technological advances, little is known about the
molecular biology and biochemistry of these flukes. We present the
draft genome of Fasciola gigantica for
the first time. The assembled draft genome has a size of ∼1.04
Gb with an N50 and N90 of 129 and 149 kb, respectively. A total of
20 858 genes were predicted. The de novo repeats
identified in the draft genome were 46.85%. The pathway included all
of the genes of glycolysis, Krebs cycle, and fatty acid metabolism
but lacked the key genes of the fatty acid biosynthesis pathway. This
indicates that the fatty acid required for survival of the fluke may
be acquired from the host bile. It may be hypothesized that the relatively
larger F. gigantica genome did not
evolve through genome duplications but rather is interspersed with
many repetitive elements. The genomic information will provide a comprehensive
resource to facilitate the development of novel interventions for
fascioliasis control.
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