GAGA protein: a multi-faceted transcription factorThis paper is one of a selection of papers published in this Special Issue, entitled 27th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (4) ◽  
pp. 559-558 ◽  
Author(s):  
Nicholas L. Adkins ◽  
Thomas A. Hagerman ◽  
Philippe Georgel

The transition from transcription activation to repression is regulated at multiple levels by the DNA sequence and DNA modification to its compaction through chromatin packaging. The GAGA factor (GAF) is one of a few transcription factors that can regulate gene expression at multiple levels. It displays both activator/antirepressor and repressor activity, depending on its target genomic location. The GAF-mediated modulation of expression appears to be intimately linked with modifications of the chromatin structure. The GAF can associate with highly compacted heterochromatin, contributing to gene repression, or participate in nucleosome remodeling to activate specific genes. In this review, we are attempting to elucidate the contribution(s) of the various domains of the GAF to the recruitment of its functional partners, leading to seemingly opposite functions. We surveyed the current scientific literature for evidence of GAF involvement in regulatory events associated with changes of chromatin composition or conformation.

2008 ◽  
Vol 86 (2) ◽  
pp. 178-183 ◽  
Author(s):  
Nahum Sonenberg

Translational control is an important strategy by which eukaryotic cells regulate gene expression. Translation is the last step in the flow of genetic information, and regulation at this level allows an immediate and rapid response to changes under physiological conditions. Because the processes of mRNA biogenesis, including transcription, splicing, and export to the cytoplasm, are time consuming, the use of pre-existing mRNAs via the control of translation is advantageous in many circumstances. A prime target of translational control is the initiation factor eIF4E, which recognizes the m7GpppN cap structure present at the 5′ end of all nuclear transcribed eukaryotic mRNAs. In this article I describe the discovery of eIF4E, its mechanism of action in translation initiation, and its role in the control of cancer and innate immunity.


2007 ◽  
Vol 85 (2) ◽  
pp. 203-208 ◽  
Author(s):  
Hongmei Dong ◽  
Xiaohu Xu ◽  
Mohong Deng ◽  
Xiaojun Yu ◽  
Hu Zhao ◽  
...  

The aim of the study was to prepare an active recombinant human perforin by comparing 5 candidate segments of human perforin. Full-length perforin, MAC1 (28–349 aa), MAC2 (166–369 aa), C-100, and N-60 of human perforin were selected as candidate active segments and designated, respectively, HP1, HP2, HP3, HP4, and HP5. The target genes were amplified by PCR and the products were individually subcloned into pGEM-T. The genes for HP1, HP2, HP3, and HP5 were subcloned into pET-DsbA, whereas pET-41a (+) was used as the expression vector of HP4. The fusion proteins were expressed in Escherichia coli BL21pLysS(DE3) and purified using nickel nitrilotriacetic acid (NTA) agarose affinity chromatography. The hemolysis microassay was used as an activity assay of fusion protein. From this study, we obtained the recombinant plasmids pGEM-T-HP1, -HP2, -HP3, -HP4 and -HP5, consisting of 1600, 960, 600, 300bp, and 180, respectively. From these recombinant plasmids, expression plasmids were successfully constructed and expressed in E. coli BL21pLysS(DE3). The resultant fusion proteins, affinity purified using Ni–NTA, were ~80, 58, 45, 44, and 30 kDa, respectively. The recombinant proteins were assayed for activity on hemolysis. HP2 and HP5 were the only recombinant proteins that were active in hemolysis, and the hemolytic function was concentration dependent. These results demonstrate that active recombinant forms of perforin can be synthesized in a prokaryote model. The recombinant N-60 and MAC1 (28–349 aa) of human perforin have the function of forming pores. Our study provides the experimental basis for further investigation on the application of perforin.


2006 ◽  
Vol 84 (3) ◽  
pp. 282-290 ◽  
Author(s):  
Dominique Legrand ◽  
Elisabeth Elass ◽  
Mathieu Carpentier ◽  
Joël Mazurier

The antimicrobial activities of lactoferrin (Lf) depend on its capacity to bind iron and on its direct interaction with the surface of microorganisms. Its protective effect also extends to the regulation of the host response to infections. Depending on the immune status of an individual, Lf can have anti-inflammatory properties that downregulate the immune response and prevent septic shock and damage to tissues. It also acts as a promoter of the activation, differentiation, and (or) proliferation of immune cells. Although most of the anti-inflammatory activities are correlated with the neutralization of proinflammatory molecules by Lf, the promoting activity seems to be related to a direct effect of Lf on immune cells. Although the mechanisms that govern these activities are not clearly defined, and probably differ from cell to cell, several cellular targets and possible mechanisms of action are highlighted. The majority of the molecular targets at the surface of cells are multiligand receptors but, interestingly, most of them have been reported as signaling, endocytosis, and nuclear-targeting molecules. This review focuses on the known and putative mechanisms that allow the immunoregulating effect of Lf in its interactions with immune cells.


2011 ◽  
Vol 89 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Tamara L. Caterino ◽  
Jeffrey J. Hayes

Linker histones are multifunctional proteins that are involved in a myriad of processes ranging from stabilizing the folding and condensation of chromatin to playing a direct role in regulating gene expression. However, how this class of enigmatic proteins binds in chromatin and accomplishes these functions remains unclear. Here we review data regarding the H1 structure and function in chromatin, with special emphasis on the C-terminal domain (CTD), which typically encompasses approximately half of the mass of the linker histone and includes a large excess of positively charged residues. Owing to its amino acid composition, the CTD was previously proposed to function in chromatin as an unstructured polycation. However, structural studies have shown that the CTD adopts detectable secondary structure when interacting with DNA and macromolecular crowding agents. We describe classic and recent experiments defining the function of this domain in chromatin folding and emerging data indicating that the function of this protein may be linked to intrinsic disorder.


2010 ◽  
Vol 88 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Caroline A. Ewens ◽  
Patrik Kloppsteck ◽  
Andreas Förster ◽  
Xiaodong Zhang ◽  
Paul S. Freemont

p97, also known as VCP (valosin-containing protein), is a hexameric AAA+ ATPase that participates in a variety of cellular processes. It is believed that p97 mediates these processes through the binding of various adaptor proteins. Many factors govern adaptor binding and the regulatory mechanisms are not yet well understood. Sites of phosphorylation and acetylation on p97 have been identified and such post-translational modifications may be involved in regulating p97 function. Phosphorylation and, to a lesser extent, acetylation of p97 have been shown to modify its properties — for example, by modulating adaptor binding and directing subcellular localization. These modifications have been implicated in a number of p97-mediated processes, including misfolded protein degradation, membrane fusion, and transcription factor activation. This review describes the known phosphorylation and acetylation sites on p97 and discusses their possible structural and functional implications.


2010 ◽  
Vol 88 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Tobias Haslberger ◽  
Bernd Bukau ◽  
Axel Mogk

The oligomeric AAA+ chaperones ClpB/Hsp104 mediate the reactivation of aggregated proteins, an activity that is crucial for the survival of cells during severe stress. Hsp104 is also essential for the propagation of yeast prions by severing prion fibres. Protein disaggregation depends on the cooperation of ClpB/Hsp104 with a cognate Hsp70 chaperone system. While Hsp70 chaperones are also involved in prion propagation, their precise role is much less well defined compared with its function in aggregate solubilization. Therefore, it remained unclear whether both ClpB/Hsp104 activities are based on common or different mechanisms. Novel data show that ClpB/Hsp104 uses a motor threading activity to remodel both protein aggregates and prion fibrils. Moreover, transfer of both types of substrates to the ClpB/Hsp104 processing pore site requires initial substrate interaction of Hsp70. Together these data emphasize the similarity of thermotolerance and prion propagation pathways and point to a shared mechanistic principle of Hsp70–ClpB/Hsp104-mediated solubilization of amorphous and ordered aggregates.


2009 ◽  
Vol 34 (3) ◽  
pp. 488-492 ◽  
Author(s):  
Terry E. Graham

While scientists have routinely measured muscle glycogen in many metabolic situations for over 4 decades, there is surprisingly little known regarding its regulation. In the past decade, considerable evidence has illustrated that the carbohydrate stores in muscle are not homogeneous, and it is very likely that metabolic pools exist or that each granule has independent regulation. The fundamental aspects appear to be associated with a complex set of proteins that associate with both the granule and each other in a dynamic fashion. Some of the proteins are enzymes and others play scaffolding roles. A number of the proteins can translocate, depending on the metabolic stimulus. These various processes appear to be the mechanisms that give the glycogen granule precise yet dynamic regulation. This may also allow the stores to serve as an important metabolic regulator of other metabolic events.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259846
Author(s):  
Yasuhiro Fujiwara ◽  
Yuji Tanno ◽  
Hiroki Sugishita ◽  
Yusuke Kishi ◽  
Yoshinori Makino ◽  
...  

Epigenome research has employed various methods to identify the genomic location of proteins of interest, such as transcription factors and histone modifications. A recently established method called CUT&Tag uses a Protein-A Tn5 transposase fusion protein, which cuts the genome and inserts adapter sequences nearby the target protein. Throughout most of the CUT&Tag procedure, cells are held on concanavalin A (con A)-conjugated magnetic beads. Proper holding of cells would be decisive for the accessibility of Tn5 to the chromatin, and efficacy of the procedure of washing cells. However, BioMag®Plus ConA magnetic beads, used in the original CUT&Tag protocol, often exhibit poor suspendability and severe aggregation. Here, we compared the BioMag beads and Dynabeads® magnetic particles of which conjugation of con A was done by our hands, and examined the performance of these magnetic beads in CUT&Tag. Among tested, one of the Dynabeads, MyOne-T1, kept excessive suspendability in a buffer even after overnight incubation. Furthermore, the MyOne-T1 beads notably improved the sensitivity in CUT&Tag assay for H3K4me3. In conclusion, the arrangement and the selection of MyOne-T1 refine the suspendability of beads, which improves the association of chromatin with Tn5, which enhances the sensitivity in CUT&Tag assay.


2020 ◽  
Author(s):  
Flaminio Squazzoni ◽  
Giangiacomo Bravo ◽  
Pierpaolo Dondio ◽  
Mike Farjam ◽  
Ana Marusic ◽  
...  

This article examines gender bias in peer review with complete data on 145 journals in various fields of research, including about 1.7 million authors and 740,000 referees. We reconstructed three possible sources of bias, i.e., the editorial selection of referees, referee recommendations, and editorial decisions, and examined all their possible relationships. In line with previous research, we found that editors were sensitive to gender homophily in that they tended to match authors and referee by gender systematically. Results showed that in general manuscripts written by women as solo authors or co-authored by women are treated even more favorably by referees and editors. This is especially so in biomedicine and health journals, whereas women were treated relatively less favorably in social science & humanities journals, i.e., the field in which the ratio of female authors was the highest in our sample. Although with some caveat, our findings suggest that peer review and editorial processes in scholarly journals do not penalize manuscripts by women. However, considering the complex social nature of gender prejudices, journals should increase gender diversity among reviewers and editors as a means of correcting signals potentially biasing the perceptions of authors and referees.


2021 ◽  
pp. 82-83
Author(s):  
Oluwole Gbolagunte Ajao ◽  
Adekola Alao

SUMMARY: The peer review process has been regarded as an essential part of accepting or rejecting a paper for publication since 1752 when the process was started by The Royal Society of London in the publication entitled “Philosophical Transactions”. In developing countries, one of the primary reasons for submitting pieces for publication is to support promotion in universities. In fact, the argument can be made that the only reason for publishing in developing countries is for faculty promotion. Despite the peer review process being standard practice for scientic journals, many of the research publications on COVID-19 were not subjected to the peer review system. In fact, numerous publications were pre-prints and papers shared by researchers online which were not peer reviewed, yet they were accepted and published by scientic journals in developing nations. When authors start to lose condence in the peer review process of a journal, they are not likely to submit their research work to such journals and this can lead to a diminished impact and reputation of such journals. Additionally, the selection of the assessors by the Editor-in -Chief is usually from the academic space of the editor and from the colleagues of the editor that usually share the editor's view. Contrary to what some editors in the developing countries believe, medical and academic administrative positions do not necessarily result in expertise in the peer review process. An editor can easily identify a poor assessment of an article, from the vitriolic feed-back of the author to the editor about an assessor when a paper is not recommended for publication. This paper provides evidence of and outlines the possible reasons that the peer review process is substandard in developing countries.


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