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Targeting E3 ubiquitin ligases and their adaptors as a therapeutic strategy for metabolic diseases
Jeong Yelin,Oh Ah-Reum,Jung Young Hoon,Gi HyunJoon,Kim Young Un,Kim KyeongJin 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Posttranslational modification of proteins via ubiquitination determines their activation, translocation, dysregulation, or degradation. This process targets a large number of cellular proteins, affecting all biological pathways involved in the cell cycle, development, growth, and differentiation. Thus, aberrant regulation of ubiquitination is likely associated with several diseases, including various types of metabolic diseases. Among the ubiquitin enzymes, E3 ubiquitin ligases are regarded as the most influential ubiquitin enzymes due to their ability to selectively bind and recruit target substrates for ubiquitination. Continued research on the regulatory mechanisms of E3 ligases and their adaptors in metabolic diseases will further stimulate the discovery of new targets and accelerate the development of therapeutic options for metabolic diseases. In this review, based on recent discoveries, we summarize new insights into the roles of E3 ubiquitin ligases and their adaptors in the pathogenesis of metabolic diseases by highlighting recent evidence obtained in both human and animal model studies.
Molecular analysis of <i>B</i> mating type diversity in <i>Lentinula edodes</i>
Ha, Byeongsuk,Moon, Yoon Jung,Song, Yelin,Kim, Sinil,Kim, Minseek,Yoon, Cheol-Won,Ro, Hyeon-Su Elsevier 2019 Scientia horticulturae Vol.243 No.-
<P><B>Abstract</B></P> <P>Pheromone and pheromone receptor genes in <I>B</I> mating type locus constitute <I>B</I> mating type of fungi belonging to Basidiomycota. In <I>Lentinula edodes</I>, multiple <I>B</I> mating types have been suggested based on genome sequence analysis and mating assay. Here we report finding of new alleles of pheromones (<I>phb</I>s) and pheromone receptors (<I>rcb</I>s) to constitute five alleles of <I>rcb1</I> (<I>rcb1-1</I>∼<I>rcb1-5</I>) with nine associated <I>phbs</I> in <I>Bα</I> sublocus and three alleles of <I>rcb2</I> (<I>rcb2-1</I>∼<I>rcb2-3</I>) with five associated <I>phbs</I> in <I>Bβ</I> sublocus. Each <I>rcb</I> was primarily associated with two <I>phbs</I>. Each <I>phb</I>-<I>rcb</I> pair was recurrently discovered as a distinct unit in various monokarytotic and dikaryotic strains, regardless of subloci. This allowed us to propose 15 <I>B</I> mating types through combinations of five <I>Bα</I> and three <I>Bβ</I> subloci. PCR analyses with primer sets probing alleles of <I>rcb1</I> and <I>rcb2</I> demonstrated that all monokaryotic strains contained one of the five <I>rcb1</I>s and one of the three <I>rcb2</I>s representing <I>Bα</I> and <I>Bβ</I> subloci, respectively, thereby enabling designation of their <I>B</I> mating types via combinations of <I>Bα</I> and <I>Bβ</I>. PCR analyses also revealed the presence of one or two alleles of <I>rcb1</I> and <I>rcb2</I> representing <I>B</I> mating type of each nuclei in dikaryotic cytoplasm. Further investigation of 111 dikaryotic strains, including 83 cultivated and 28 wild strains collected from East Asia, revealed that <I>B8</I> and <I>B11</I> mating types constructed by <I>rcb1-3</I> + <I>rcb2-2</I> and <I>rcb1-4</I> + <I>rcb2-2</I>, respectively, were more prevalent in cultivated strains. In <I>B</I> mating type pairs representing each nucleus in dikaryons, <I>B2B12</I>, <I>B4B8</I>, and <I>B8B11</I> were frequently occurring pairs in cultivated strains while none of them was found in wild strains. Such prevalence indicates that certain nuclei have been preferentially selected in the generation of cultivated strains. Our findings shed new light on the construction of <I>B</I> mating type in <I>L. edodes</I> and provide practical tools in the breeding of new cultivars.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The <I>B</I> mating type locus of <I>L. edodes</I> consists of multiallelic pheromone and receptor genes. </LI> <LI> 5 <I>rcb1</I>s and 3 <I>rcb2</I>s constitute <I>Bα</I> and <I>Bβ</I> subloci, respectively, with 14 <I>phb</I>s. </LI> <LI> Each <I>rcb</I> pairs with distinct <I>phb</I>(s) and thus found as a <I>phb-rcb</I> unit in sublocus. </LI> <LI> Combinatorial assortment of <I>Bα</I> and <I>Bβ</I> subloci generates fifteen <I>B</I> mating types. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>