Faculty Opinions recommendation of Disorder-associated mutations lead to functional inactivation of neuroligins.

2004 ◽  
Author(s):  
L. Alison McInnes
Keyword(s):  
Functional Inactivation

scholarly journals Roles of pRB in the Regulation of Nucleosome and Chromatin Structures

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Chiharu Uchida
Keyword(s):  
Target Genes ◽  
Chromosome Instability ◽  
Cancer Therapies ◽  
Induce Cell Cycle Arrest ◽  
Cellular Events ◽  
Cycle Arrest ◽  
Histone Modifiers ◽  
Physical Interactions ◽  
Functional Inactivation

Retinoblastoma protein (pRB) interacts with E2F and other protein factors to play a pivotal role in regulating the expression of target genes that induce cell cycle arrest, apoptosis, and differentiation. pRB controls the local promoter activity and has the ability to change the structure of nucleosomes and/or chromosomes via histone modification, epigenetic changes, chromatin remodeling, and chromosome organization. Functional inactivation of pRB perturbs these cellular events and causes dysregulated cell growth and chromosome instability, which are hallmarks of cancer cells. The role of pRB in regulation of nucleosome/chromatin structures has been shown to link to tumor suppression. This review focuses on the ability of pRB to control nucleosome/chromatin structures via physical interactions with histone modifiers and chromatin factors and describes cancer therapies based on targeting these protein factors.

scholarly journals Biofunctional Peptide FNIII14: Therapeutic Potential

Encyclopedia ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 350-359
Author(s):  
Motomichi Fujita ◽  
Manabu Sasada ◽  
Takuya Iyoda ◽  
Satoshi Osada ◽  
Hiroaki Kodama ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Extracellular Matrix ◽  
Conformational Changes ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Malignant Tumors ◽  
Β1 Integrin ◽  
Inactive Form ◽  
Functional Inactivation ◽  
Organ Fibrosis

Biofunctional peptide FNIII14, which is derived from the 14th fibronectin (FN) type III-like (FN-III) repeat of FN molecule, is capable of inhibiting cell adhesion to the extracellular matrix (ECM). This functional site is usually buried within the molecular structure of FN, but can be exposed by conformational changes and proteolytic cleavage. Peptide FNIII14 can induce a conformational change in β1-integrin from the active to the inactive form, causing functional inactivation. Based on this anti-adhesive activity, peptide FNIII14 exhibits therapeutic potential for several diseases such as metabolic diseases, organ fibrosis, and malignant tumors. Peptide FNIII14 blocks integrin-mediated signaling by a mechanism entirely distinct from that of conventional antagonisitic peptides, including Arg-Gly-Asp peptides that competitively inhibit the ECM binding of integrin.

scholarly journals Cytoplasmic Recycling of 60S Preribosomal Factors Depends on the AAA Protein Drg1

2007 ◽  
Vol 27 (19) ◽  
pp. 6581-6592 ◽  
Author(s):  
Brigitte Pertschy ◽  
Cosmin Saveanu ◽  
Gertrude Zisser ◽  
Alice Lebreton ◽  
Martin Tengg ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Nuclear Export ◽  
Ribosome Biogenesis ◽  
Dominant Negative ◽  
Cytoplasmic Localization ◽  
Atpase Domain ◽  
Aaa Atpase ◽  
Cytoplasmic Accumulation ◽  
Functional Inactivation ◽  
Aaa Protein

ABSTRACT Allelic forms of DRG1/AFG2 confer resistance to the drug diazaborine, an inhibitor of ribosome biogenesis in Saccharomyces cerevisiae. Our results show that the AAA-ATPase Drg1 is essential for 60S maturation and associates with 60S precursor particles in the cytoplasm. Functional inactivation of Drg1 leads to an increased cytoplasmic localization of shuttling pre-60S maturation factors like Rlp24, Arx1, and Tif6. Surprisingly, Nog1, a nuclear pre-60S factor, was also relocalized to the cytoplasm under these conditions, suggesting that it is a previously unsuspected shuttling preribosomal factor that is exported with the precursor particles and very rapidly reimported. Proteins that became cytoplasmic under drg1 mutant conditions were blocked on pre-60S particles at a step that precedes the association of Rei1, a later-acting preribosomal factor. A similar cytoplasmic accumulation of Nog1 and Rlp24 in pre-60S-bound form could be seen after overexpression of a dominant-negative Drg1 variant mutated in the D2 ATPase domain. We conclude that the ATPase activity of Drg1 is required for the release of shuttling proteins from the pre-60S particles shortly after their nuclear export. This early cytoplasmic release reaction defines a novel step in eukaryotic ribosome maturation.

The effect of the heat shock response on ultrastructure of the centrosome of Drosophila cultured cells in interphase: possible relation with changes in the chemical state of calcium.

1993 ◽  
Vol 71 (11-12) ◽  
pp. 507-517 ◽  
Author(s):  
Christiane Marcaillou ◽  
Alain Debec ◽  
Sylvie Lauverjat ◽  
Armelle Saihi
Keyword(s):  
Heat Shock ◽  
Heat Shock Response ◽  
Cultured Cells ◽  
Chemical State ◽  
Ultrastructural Organization ◽  
Heat Shock Stress ◽  
Shock Response ◽  
Pericentriolar Material ◽  
Functional Inactivation ◽  
Drosophila Embryos

Previous observations have shown that the heat shock response affects the centrosome function. We compared the ultrastructural organization of the centrosome in control (23 °C) and heat-shocked (37 °C, 50 min) interphase Drosophila cells to detect the nature of the lesions that could alter this organelle. The centrosome apparatus showed only minor modifications after the stress and the architecture of the centrioles appeared unaffected. The main difference concerned the organization of pericentriolar material which appeared more condensed and clotted. In extreme cases this material seemed to collapse on the centrioles. Recent reports proposed that Ca2+ concentrations could modify the distribution of pericentriolar material. In this study, we measured the changes in total and bound calcium in control or heat-shocked cell samples. The hyperthermia stress induced an increase of about 80% in global calcium. However, there was a decrease of about 50% in bound calcium. A heat shock stress seemed therefore to promote a change from the bound to the free state for a noticeable proportion of the element. As a preliminary hypothesis, these changes in the chemical state of calcium could be related to alterations in the pericentriolar material and thus with the functional inactivation of the centrosome. This view is also supported by calcium analysis on early Drosophila embryos. Contrary to cultured cells, Drosophila embryos did not present a stress inactivation of centrosomes. Equally, a heat shock did not disturb the bound calcium level in embryos.Key words: Centrosome, ultrastructure, calcium, heat shock, Drosophila.

scholarly journals Disorder-associated mutations lead to functional inactivation of neuroligins

2004 ◽  
Vol 13 (14) ◽  
pp. 1471-1477 ◽  
Author(s):  
Ben Chih ◽  
Shehla Khan Afridi ◽  
Lorraine Clark ◽  
Peter Scheiffele
Keyword(s):  
Functional Inactivation

scholarly journals dE2F2-Independent Rescue of Proliferation in Cells Lacking an Activator dE2F1

2007 ◽  
Vol 27 (24) ◽  
pp. 8561-8570 ◽  
Author(s):  
Aaron M. Ambrus ◽  
Brandon N. Nicolay ◽  
Vanya I. Rasheva ◽  
Richard J. Suckling ◽  
Maxim V. Frolov
Keyword(s):  
Cell Cycle ◽  
Morphogenetic Furrow ◽  
Independent Manner ◽  
Dead Box ◽  
Cycle Arrest ◽  
Eye Disc ◽  
Severe Reduction ◽  
Functional Inactivation ◽  
Mutant Cells ◽  
Dependent Mechanism

ABSTRACT In Drosophila melanogaster, the loss of activator de2f1 leads to a severe reduction in cell proliferation and repression of E2F targets. To date, the only known way to rescue the proliferation block in de2f1 mutants was through the inactivation of dE2F2. This suggests that dE2F2 provides a major contribution to the de2f1 mutant phenotype. Here, we report that in mosaic animals, in addition to de2f2, the loss of a DEAD box protein Belle (Bel) also rescues proliferation of de2f1 mutant cells. Surprisingly, the rescue occurs in a dE2F2-independent manner since the loss of Bel does not relieve dE2F2-mediated repression. In the eye disc, bel mutant cells fail to undergo a G1 arrest in the morphogenetic furrow, delay photoreceptor recruitment and differentiation, and show a reduction of the transcription factor Ci155. The down-regulation of Ci155 is important since it is sufficient to partially rescue proliferation of de2f1 mutant cells. Thus, mutation of bel relieves the dE2F2-mediated cell cycle arrest in de2f1 mutant cells through a novel Ci155-dependent mechanism without functional inactivation of the dE2F2 repressor.

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