activity regulation
Recently Published Documents


TOTAL DOCUMENTS

240
(FIVE YEARS 59)

H-INDEX

34
(FIVE YEARS 3)

2022 ◽  
pp. 2102329
Author(s):  
Ning Liu ◽  
Lianghan Zhu ◽  
Honghao Sun ◽  
Zhanwei Zhou ◽  
Jingwen Dong ◽  
...  

2021 ◽  
pp. 1-10
Author(s):  
Kristin A. Marks ◽  
Maria F. Fernandes ◽  
Kalsha H. Diaguarachchige De Silva ◽  
Michelle V. Tomczewski ◽  
Ken D. Stark ◽  
...  

Delta-6-desaturase (D6D) activity is deficient in MCF-7 and other cancer cell lines, but it is not explained by FADS2 gene mutations. This deficient activity was not ameliorated by induction of the FADS2 gene; therefore, we hypothesized that some of the induced FADS2 transcript variants (tv) may play a negative regulatory role. FADS2_tv1 is the reference FADS2 tv, coding for full-length D6D isoform 1 (D6D-iso1), and alternative transcriptional start sites result in FADS2_tv2 and FADS2_tv3 variants encoding D6D-iso2 and D6D-iso3 isoforms, respectively, which lack the catalytically critical N-terminal domain. In MCF-7 cells, FADS2_tv2 and FADS2_tv3 were expressed at significantly higher levels than FADS2_tv1. Overexpression of FADS2_tv2 in HEK293 cells confirmed that D6D-iso2 is non-functional, and co-transfection demonstrated a dominant-negative role for D6D-iso2 in D6D-iso1 activity regulation. FADS2_tv2 was expressed at higher levels than FADS2_tv1 in HeLa, MDA-MB-435, MCF-10 A, and HT-29 cells, but at lower levels in A549, MDA-MB-231, and LNCaP cells. Overexpression studies indicated roles for FADS2 variants in proliferation and apoptosis regulation, which were also cell-line specific. Increased FADS2_tv2 expression provides a new mechanism to help explain deficient D6D activity in MCF-7 and other cancer cell lines, but it is not a hallmark of malignant cells.


Catalysts ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1123
Author(s):  
Guangchun Song ◽  
Nan Cheng ◽  
Junjie Zhang ◽  
Huixian Huang ◽  
Yanfang Yuan ◽  
...  

Nanoscale cerium oxide has excellent catalytic performance due to its unique surface properties and has very important applications in various fields. In this paper, the synthesis methods, catalytic mechanism and activity regulation of nanoscale cerium oxide in recent years are reviewed. Secondly, the application of cerium oxide in the detection of organic and inorganic molecules is summarized, and its latest progress and applications in antibacterial, antioxidant and anticancer are discussed. Finally, the future development prospect of nanoscale cerium oxide is summarized and prospected.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1701
Author(s):  
Lorenz Weidenauer ◽  
Manfredo Quadroni

Hsp90β is a major chaperone involved in numerous cellular processes. Hundreds of client proteins depend on Hsp90β for proper folding and/or activity. Regulation of Hsp90β is critical to coordinate its tasks and is mediated by several post-translational modifications. Here, we focus on two phosphorylation sites located in the charged linker region of human Hsp90β, Ser226 and Ser255, which have been frequently reported but whose function remains unclear. Targeted measurements by mass spectrometry indicated that intracellular Hsp90β is highly phosphorylated on both sites (>90%). The level of phosphorylation was unaffected by various stresses (e.g., heat shock, inhibition with drugs) that impact Hsp90β activity. Mutating the two serines to alanines increased the amount of proteins interacting with Hsp90β globally and increased the sensitivity to tryptic cleavage in the C-terminal domain. Further investigation revealed that phosphorylation on Ser255 and to a lesser extent on Ser226 is decreased in the conditioned medium of cultured K562 cells, and that a non-phosphorylatable double alanine mutant was secreted more efficiently than the wild type. Overall, our results show that phosphorylation events in the charged linker regulate both the interactions of Hsp90β and its secretion, through changes in the conformation of the chaperone.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yingying Liu ◽  
Yanjun Zhang ◽  
Han Xue ◽  
Mi Cao ◽  
Guohui Bai ◽  
...  

AbstractSubstitution of lysine 36 with methionine in histone H3.3 (H3.3K36M) is an oncogenic mutation that inhibits SETD2-mediated histone H3K36 tri-methylation in tumors. To investigate how the oncohistone mutation affects the function of SETD2 at the nucleosome level, we determined the cryo-EM structure of human SETD2 associated with an H3.3K36M nucleosome and cofactor S-adenosylmethionine (SAM), and revealed that SETD2 is attached to the N-terminal region of histone H3 and the nucleosome DNA at superhelix location 1, accompanied with the partial unwrapping of nucleosome DNA to expose the SETD2-binding site. These structural features were also observed in the previous cryo-EM structure of the fungal Set2–nucleosome complex. By contrast with the stable association of SETD2 with the H3.3K36M nucleosome, the EM densities of SETD2 could not be observed on the wild-type nucleosome surface, suggesting that the association of SETD2 with wild-type nucleosome might be transient. The linker histone H1, which stabilizes the wrapping of nucleosome DNA at the entry/exit sites, exhibits an inhibitory effect on the activities of SETD2 and displays inversely correlated genome distributions with that of the H3K36me3 marks. Cryo-EM analysis of yeast H3K36 methyltransferase Set2 complexed with nucleosomes further revealed evolutionarily conserved structural features for nucleosome recognition in eukaryotes, and provides insights into the mechanism of activity regulation. These findings have advanced our understanding of the structural basis for the tumorigenesis mechanism of the H3.3K36M mutation and highlight the effect of nucleosome conformation on the regulation of histone modification.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tjaša Plaper ◽  
Jana Aupič ◽  
Petra Dekleva ◽  
Fabio Lapenta ◽  
Mateja Manček Keber ◽  
...  

AbstractCoiled-coil (CC) dimer-forming peptides are attractive designable modules for mediating protein association. Highly stable CCs are desired for biological activity regulation and assay. Here, we report the design and versatile applications of orthogonal CC dimer-forming peptides with a dissociation constant in the low nanomolar range. In vitro stability and specificity was confirmed in mammalian cells by enzyme reconstitution, transcriptional activation using a combination of DNA-binding and a transcriptional activation domain, and cellular-enzyme-activity regulation based on externally-added peptides. In addition to cellular regulation, coiled-coil-mediated reporter reconstitution was used for the detection of cell fusion mediated by the interaction between the spike protein of pandemic SARS-CoV2 and the ACE2 receptor. This assay can be used to investigate the mechanism of viral spike protein-mediated fusion or screening for viral inhibitors under biosafety level 1 conditions.


Sign in / Sign up

Export Citation Format

Share Document