scholarly journals The Balance between Mono- and NEDD8-Chains Controlled by NEDP1 upon DNA Damage Is a Regulatory Module of the HSP70 ATPase Activity

Cell Reports ◽  
2019 ◽  
Vol 29 (1) ◽  
pp. 212-224.e8 ◽  
Author(s):  
Aymeric P. Bailly ◽  
Aurelien Perrin ◽  
Marina Serrano-Macia ◽  
Chantal Maghames ◽  
Orsolya Leidecker ◽  
...  
Keyword(s):  
Dna Damage ◽  
Atpase Activity ◽  
Regulatory Module

scholarly journals The NEDD8 cycle controlled by NEDP1 upon DNA damage is a regulatory module of the HSP70 ATPase activity

2019 ◽  
Author(s):  
Aymeric P. Bailly ◽  
Aurelien Perrin ◽  
Marina Serrano-Macia ◽  
Chantal Maghames ◽  
Orsolya Leidecker ◽  
...  
Keyword(s):  
Dna Damage ◽  
Atpase Activity ◽  
Apoptosis Induction ◽  
Regulatory Module ◽  
Hsp70 Chaperone ◽  
Response To Stress ◽  
Conjugating Enzymes ◽  
Induced Apoptosis

SummaryUbiquitin and ubiquitin-like chains are finely balanced by the action of conjugating and de-conjugating enzymes. Alterations in this balance trigger signalling events required for the response to stress conditions and are often observed in pathologies. How such changes are detected is not well-understood. We show that upon DNA damage the induction of the de-NEDDylating enzyme NEDP1 restricts the formation of poly-NEDD8 chains, mainly through lysines K11/K48. This promotes APAF1 oligomerisation and apoptosis induction, a step that requires the HSP70 ATPase activity. We found that HSP70 binds to NEDD8 and in vitro, mono-NEDD8 stimulates the ATPase activity of HSP70, counteracted upon poly-NEDDylation. This effect is independent of NEDD8 conjugation onto substrates. The studies identify the HSP70 chaperone as sensor of changes in the NEDD8 cycle, providing mechanistic insights for a cytoplasmic role of NEDD8 in the DNA damage induced apoptosis. They also indicate that the balance between mono- versus poly-NEDDylation is a regulatory module of HSP70 function. The above findings may be important in tumorigenesis, as we find that NEDP1 levels are downregulated in Hepatocellular Carcinoma with concomitant accumulation of NEDD8 conjugates.

scholarly journals Association of the circadian factor Period 2 to p53 influences p53's function in DNA-damage signaling

2015 ◽  
Vol 26 (2) ◽  
pp. 359-372 ◽  
Author(s):  
Tetsuya Gotoh ◽  
Marian Vila-Caballer ◽  
Jingjing Liu ◽  
Samuel Schiffhauer ◽  
Carla V. Finkielstein
Keyword(s):  
Dna Damage ◽  
Target Genes ◽  
Genotoxic Stress ◽  
Negative Regulator ◽  
Transcriptional Level ◽  
Stable Form ◽  
Checkpoint Signaling ◽  
Trimeric Complex ◽  
Period 2 ◽  
Regulatory Module

Circadian period proteins influence cell division and death by associating with checkpoint components, although their mode of regulation has not been firmly established. hPer2 forms a trimeric complex with hp53 and its negative regulator Mdm2. In unstressed cells, this association leads to increased hp53 stability by blocking Mdm2-dependent ubiquitination and transcription of hp53 target genes. Because of the relevance of hp53 in checkpoint signaling, we hypothesize that hPer2 association with hp53 acts as a regulatory module that influences hp53's downstream response to genotoxic stress. Unlike the trimeric complex, whose distribution was confined to the nuclear compartment, hPer2/hp53 was identified in both cytosol and nucleus. At the transcriptional level, a reporter containing the hp21WAF1/CIP1 promoter, a target of hp53, remained inactive in cells expressing a stable form of the hPer2/hp53 complex even when treated with γ-radiation. Finally, we established that hPer2 directly acts on the hp53 node, as checkpoint components upstream of hp53 remained active in response to DNA damage. Quantitative transcriptional analyses of hp53 target genes demonstrated that unbound hp53 was absolutely required for activation of the DNA-damage response. Our results provide evidence of the mode by which the circadian tumor suppressor hPer2 modulates hp53 signaling in response to genotoxic stress.

The HSP70 chaperone as sensor of the NEDD8 cycle upon DNA damage

2021 ◽  
Author(s):  
Aymeric P. Bailly ◽  
Dimitris P. Xirodimas
Keyword(s):  
Dna Damage ◽  
Protein Quality ◽  
Atp Hydrolysis ◽  
Regulatory Modules ◽  
Chaperone Function ◽  
Regulatory Module ◽  
Essential Components ◽  
Evolutionarily Conserved ◽  
Hsp70 Chaperone ◽  
Protein Quality Control System

Molecular chaperones are essential components of the protein quality control system and maintenance of homeostasis. Heat Shock Protein 70 (HSP70), a highly evolutionarily conserved family of chaperones is a key regulator of protein folding, oligomerisation and prevents the aggregation of misfolded proteins. HSP70 chaperone function depends on the so-called ‘HSP70-cycle', where HSP70 interacts with and is released from substrates via ATP hydrolysis and the assistance of HSP70 co-factors/co-chaperones, which also provide substrate specificity. The identification of regulatory modules for HSP70 allows the elucidation of HSP70 specificity and target selectivity. Here, we discuss how the HSP70 cycle is functionally linked with the cycle of the Ubiquitin-like molecule NEDD8. Using as an example the DNA damage response, we present a model where HSP70 acts as a sensor of the NEDD8 cycle. The NEDD8 cycle acts as a regulatory module of HSP70 activity, where conversion of poly-NEDD8 chains into mono-NEDD8 upon DNA damage activates HSP70, facilitating the formation of the apoptosome and apoptosis execution.

Localization of Adenosine Triphosphatase Activity in the Phleom of Nicotiana Tabacum

1972 ◽  
Vol 30 ◽  
pp. 230-231
Author(s):  
James Cronshaw ◽  
Jamison E. Gilder
Keyword(s):  
Plasma Membrane ◽  
Atpase Activity ◽  
Adenosine Triphosphatase ◽  
Higher Plants ◽  
High Surface ◽  
Root Tip ◽  
Animal Cells ◽  
Physiological Processes ◽  
Tip Cells ◽  
Atpase Localization

Adenosine triphosphatase (ATPase) activity has been shown to be associated with numerous physiological processes in both plants and animal cells. Biochemical studies have shown that in higher plants ATPase activity is high in cell wall preparations and is associated with the plasma membrane, nuclei, mitochondria, chloroplasts and lysosomes. However, there have been only a few ATPase localization studies of higher plants at the electron microscope level. Poux (1967) demonstrated ATPase activity associated with most cellular organelles in the protoderm cells of Cucumis roots. Hall (1971) has demonstrated ATPase activity in root tip cells of Zea mays. There was high surface activity largely associated with the plasma membrane and plasmodesmata. ATPase activity was also demonstrated in mitochondria, dictyosomes, endoplasmic reticulum and plastids.

A High Resolution Cytochemical Study of Nuclear ATPase in Human Spermatozoa

1975 ◽  
Vol 33 ◽  
pp. 594-595
Author(s):  
A. Sosa ◽  
L. Calzada
Keyword(s):  
High Resolution ◽  
Atpase Activity ◽  
Nuclear Membrane ◽  
Human Sperm ◽  
Sperm Nucleus ◽  
Human Spermatozoa ◽  
Cytochemical Study ◽  
Membrane Bound ◽  
Sperm Nuclei ◽  
Interchromatin Space

The dependence of nuclear metabolism on the function of the nuclear membrane is not well understood. Whether or not the function of the nuclear membrane is partial or totally responsible of the repressed template activity of human sperm nucleus has not at present been elucidated. One of the membrane-bound enzymatic activities which is concerned with the mechanisms whereby substances are thought to cross cell membranes is adenosintriphosphatase (ATPase). This prompted its characterization and distribution by high resolution photogrammetry on isolated human sperm nuclei. Isolated human spermatozoa nuclei were obtained as previously described. ATPase activity was demonstrated by the method of Wachstein and Meisel modified by Marchesi and Palade. ATPase activity was identified as dense and irregularly distributed granules confined to the internal leaflet of the nuclear membrane. Within the nucleus the appearance of the reaction product occurs as homogenous and dense precipitates in the interchromatin space.

Ca++-ATPase activity in the hepatopancreas cells of Oniscus asellus

1992 ◽  
Vol 50 (1) ◽  
pp. 820-821
Author(s):  
G.M. Vernon ◽  
A. Surace ◽  
R. Witkus
Keyword(s):  
B Cells ◽  
Epithelial Cell ◽  
Atpase Activity ◽  
Calcium Transport ◽  
Carcinus Maenas ◽  
Cell Types ◽  
Molt Cycle ◽  
Copper And Zinc

The hepatopancreas consists of a pair of bilobed tubules comprised of two epithelial cell types. S cells are absorptive and accumulate metals such as copper and zinc. Ca++ concentrations vary between the S and B cells and during the molt cycle. Roer and Dillaman implicated Ca++-ATPase in calcium transport during molting in Carcinus maenas. This study was undertaken to compare the localization of Ca++-ATPase activity in the S and B cells during intermolt.

1576: Prediction of Spermatozoal DNA Damage by a Novel Semen Quality Score

2004 ◽  
Vol 171 (4S) ◽  
pp. 416-416
Author(s):  
Tamer M. Said ◽  
Shyam Allamaneni ◽  
Kiran P. Nallella ◽  
Rakesh K. Sharma ◽  
Sijo J. Parekattil ◽  
...  
Keyword(s):  
Dna Damage ◽  
Semen Quality ◽  
Quality Score
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