Role of non-electrostatic forces in antimicrobial potency of a dengue-virus derived fusion peptide VG16KRKP: Mechanistic insight into the interfacial peptide-lipid interactions

The chromatoid body (CB) is a specific cloud-like structure in the cytoplasm of haploid spermatids. Recent findings indicate that CB is identified as a male germ cell-specific RNA storage and processing center, but its function has remained elusive for decades. In somatic cells, KH-type splicing regulatory protein (KSRP) is involved in regulating gene expression and maturation of select microRNAs (miRNAs). However, the function of KSRP in spermatogenesis remains unclear. In this study, we showed that KSRP partly localizes in CB, as a component of CB. KSRP interacts with proteins (mouse VASA homolog (MVH), polyadenylate-binding protein 1 (PABP1) and polyadenylate-binding protein 2 (PABP2)), mRNAs (Tnp2 and Odf1) and microRNAs (microRNA-182) in mouse CB. Moreover, KSRP may regulate the integrity of CB via DDX5-miRNA-182 pathway. In addition, we found abnormal expressions of CB component in testes of Ksrp-knockout mice and of patients with hypospermatogenesis. Thus, our results provide mechanistic insight into the role of KSRP in spermatogenesis.

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Mechanistic insight into the role of metformin in Alzheimer's disease

Life Sciences ◽

10.1016/j.lfs.2021.120299 ◽

2022 ◽

pp. 120299

Author(s):

Mehdi Sanati ◽

Samaneh Aminyavari ◽

Amir R. Afshari ◽

Amirhossein Sahebkar

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mechanistic Insight ◽

Insight Into

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Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation

Nature Communications ◽

10.1038/s41467-019-12551-5 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 4

Author(s):

Brianna J. Klein ◽

Suk Min Jang ◽

Catherine Lachance ◽

Wenyi Mi ◽

Jie Lyu ◽

...

Keyword(s):

Posttranslational Modification ◽

Memory Impairment ◽

Target Genes ◽

Epigenetic Mark ◽

Mechanistic Insight ◽

Genomic Analyses ◽

Insight Into

Abstract Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORFDPF). The crystal structure of MORFDPF in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORFDPF in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORFDPF with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription.

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NUMB regulates the endocytosis and activity of the anaplastic lymphoma kinase in an isoform-specific manner

Journal of Molecular Cell Biology ◽

10.1093/jmcb/mjz003 ◽

2019 ◽

Vol 11 (11) ◽

pp. 994-1005 ◽

Cited By ~ 2

Author(s):

Ran Wei ◽

Xuguang Liu ◽

Courtney Voss ◽

Wentao Qin ◽

Lina Dagnino ◽

...

Keyword(s):

Cell Fate ◽

Receptor Tyrosine Kinase ◽

Anaplastic Lymphoma Kinase ◽

Degradation Pathway ◽

Anaplastic Lymphoma ◽

Mechanistic Insight ◽

Evolutionarily Conserved ◽

Specific Manner ◽

Insight Into

Abstract NUMB is an evolutionarily conserved protein that plays an important role in cell adhesion, migration, polarity, and cell fate determination. It has also been shown to play a role in the pathogenesis of certain cancers, although it remains controversial whether NUMB functions as an oncoprotein or tumor suppressor. Here, we show that NUMB binds to anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase aberrantly activated in several forms of cancer, and this interaction regulates the endocytosis and activity of ALK. Intriguingly, the function of the NUMB–ALK interaction is isoform-dependent. While both p66-NUMB and p72-NUMB isoforms are capable of mediating the endocytosis of ALK, the former directs ALK to the lysosomal degradation pathway, thus decreasing the overall ALK level and the downstream MAP kinase signal. In contrast, the p72-NUMB isoform promotes ALK recycling back to the plasma membrane, thereby maintaining the kinase in its active state. Our work sheds light on the controversial role of different isoforms of NUMB in tumorigenesis and provides mechanistic insight into ALK regulation.

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Mechanistic insight into the role of immunocastration on eliminating skatole in boars

Theriogenology ◽

10.1016/j.theriogenology.2019.03.017 ◽

2019 ◽

Vol 131 ◽

pp. 32-40 ◽

Cited By ~ 3

Author(s):

Xingfa Han ◽

Min Zhou ◽

Xiaohan Cao ◽

Xiaogang Du ◽

Fengyan Meng ◽

...

Keyword(s):

Mechanistic Insight ◽

Insight Into

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Mechanistic insight into WEB-2170-induced apoptosis in human acute myelogenous leukemia cells: The crucial role of PTEN

Experimental Hematology ◽

10.1016/j.exphem.2009.07.002 ◽

2009 ◽

Vol 37 (10) ◽

pp. 1176-1185.e21 ◽

Cited By ~ 13

Author(s):

Cristina Cellai ◽

Anna Laurenzana ◽

Elisa Bianchi ◽

Sara Sdelci ◽

Rossella Manfredini ◽

...

Keyword(s):

Acute Myelogenous Leukemia ◽

Crucial Role ◽

Myelogenous Leukemia ◽

Leukemia Cells ◽

Mechanistic Insight ◽

Acute Myelogenous ◽

Induced Apoptosis ◽

Insight Into

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Enantioselective Reductive Coupling of 1,3-Enynes to Heterocyclic Aromatic Aldehydes and Ketones via Rhodium-Catalyzed Asymmetric Hydrogenation: Mechanistic Insight into the Role of Broensted Acid Additives.

ChemInform ◽

10.1002/chin.200717093 ◽

2007 ◽

Vol 38 (17) ◽

Author(s):

Venukrishnan Komanduri ◽

Michael J. Krische

Keyword(s):

Asymmetric Hydrogenation ◽

Aromatic Aldehydes ◽

Reductive Coupling ◽

Mechanistic Insight ◽

Aldehydes And Ketones ◽

Insight Into

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Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1605265113 ◽

2016 ◽

Vol 113 (39) ◽

pp. 10992-10997 ◽

Cited By ~ 14

Author(s):

Erik P. Rader ◽

Rolf Turk ◽

Tobias Willer ◽

Daniel Beltrán ◽

Kei-ichiro Inamori ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscular Dystrophy ◽

Pathological Feature ◽

Passive Tension ◽

Lengthening Contractions ◽

Mechanistic Insight ◽

The Stability ◽

Muscle Biopsies ◽

Insight Into

Dystroglycan (DG) is a highly expressed extracellular matrix receptor that is linked to the cytoskeleton in skeletal muscle. DG is critical for the function of skeletal muscle, and muscle with primary defects in the expression and/or function of DG throughout development has many pathological features and a severe muscular dystrophy phenotype. In addition, reduction in DG at the sarcolemma is a common feature in muscle biopsies from patients with various types of muscular dystrophy. However, the consequence of disrupting DG in mature muscle is not known. Here, we investigated muscles of transgenic mice several months after genetic knockdown of DG at maturity. In our study, an increase in susceptibility to contraction-induced injury was the first pathological feature observed after the levels of DG at the sarcolemma were reduced. The contraction-induced injury was not accompanied by increased necrosis, excitation–contraction uncoupling, or fragility of the sarcolemma. Rather, disruption of the sarcomeric cytoskeleton was evident as reduced passive tension and decreased titin immunostaining. These results reveal a role for DG in maintaining the stability of the sarcomeric cytoskeleton during contraction and provide mechanistic insight into the cause of the reduction in strength that occurs in muscular dystrophy after lengthening contractions.

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