Transcriptional control by chromosome-associated protein phosphatase-1

2005 ◽  
Vol 33 (6) ◽  
pp. 1444-1446 ◽  
Author(s):  
D. Bennett

Tight regulation of gene expression is critical for cells to respond normally to physiological and environmental cues and to allow cell specialization. Reversible phosphorylation of key structural and regulatory proteins, from histones to the transcriptional machinery, is acknowledged to be an important mechanism of regulating spatial and temporal patterns of gene expression. PP1 (protein phosphatase-1), a major class of serine/threonine protein phosphatase, is found at many sites on Drosophila polytene chromosomes where it is involved in controlling gene expression and chromatin structure. PP1 is targeted to different chromosomal loci through interaction with a variety of different regulatory subunits, which modify PP1's activity towards specific substrates. This mini-review gives an overview of known chromosome-associated PP1 complexes, their role in transcriptional control and the prospects for future analysis.


2013 ◽  
Vol 450 (2) ◽  
pp. 311-320 ◽  
Author(s):  
Sevil Zencir ◽  
Adam Sike ◽  
Melanie J. Dobson ◽  
Ferhan Ayaydin ◽  
Imre Boros ◽  
...  

ADA (alteration/deficiency in activation) 3 is a conserved component of several transcriptional adaptor and HAT (histone acetyltransferase) complexes that regulate RNA polymerase II-mediated gene expression. Within the HAT complexes ADA3 is associated with ADA2 and the HAT GCN5 (general control non-repressed 5). ADA3 plays roles in diverse cellular processes and also in malignancies by modulating GCN5 catalytic activity and/or by interactions with other regulators. To gain a better understanding of ADA3 function, we used a yeast two-hybrid approach to screen a human fetal cDNA library for proteins that interacted with hADA3 (human ADA3). We identified three novel hADA3-interacting partners, a transcriptional regulator, AATF (apoptosis-antagonizing transcription factor), and regulatory subunits of the PP1 (protein phosphatase 1) and PP2A (protein phosphatase 2A) [PPP1R7 (PP1 regulatory subunit 7) and PPP2R5D (PP2A 56 kDa regulatory subunit δ isoform) respectively]. Analysis of truncated versions of hADA3 indicated that the C-terminal ADA2-interacting domain was not required for these interactions. Fluorescent microscopy analysis and co-immunoprecipitation provided support for the co-localization and interaction of hADA3 with these proteins in human cells. Expression of the interacting proteins altered expression of an hADA3-regulated reporter gene, suggesting functional consequences for the interactions. The detected interactions of hADA3 might extend the spectrum of mechanisms by which ADA3 can contribute to the regulation of gene expression and shed light on processes mediated by these newly identified ADA3 partners.



2020 ◽  
Author(s):  
Shahan Mamoor

Glioblastoma multiforme is an aggressive brain cancer with few treatment options and poor survival outcomes (1, 2). We used a public dataset (3) containing the gene expression information of tumors from 17 patients diagnosed with glioblastoma and compared it to the gene expression information from the non-cancerous, healthy brain tissue from 8 individuals as a reference control, to understand what is most different between the transcriptional behavior of glioblastoma tumors relative to the tissue it arises from. We found that protein phosphatase PPM1B and three protein phosphatase regulatory subunits were among the genes whose expression was most different between glioblastoma tumors and “normal” brain tissue. The fact that multiple phosphatase regulatory genes are expressed at significantly lower levels in glioblastoma tumors suggests that alteration of substrate phosphorylation might be an important event in glioblastoma formation, maintenance or progression.



2021 ◽  
Vol 8 ◽  
Author(s):  
Gustavo D. Campagnaro ◽  
Edward Nay ◽  
Michael J. Plevin ◽  
Angela K. Cruz ◽  
Pegine B. Walrad

A large number of eukaryotic proteins are processed by single or combinatorial post-translational covalent modifications that may alter their activity, interactions and fate. The set of modifications of each protein may be considered a “regulatory code”. Among the PTMs, arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), can affect how a protein interacts with other macromolecules such as nucleic acids or other proteins. In fact, many RNA-binding (RBPs) proteins are targets of PRMTs. The methylation status of RBPs may affect the expression of their bound RNAs and impact a diverse range of physiological and pathological cellular processes. Unlike most eukaryotes, Kinetoplastids have overwhelmingly intronless genes that are arranged within polycistronic units from which mature mRNAs are generated by trans-splicing. Gene expression in these organisms is thus highly dependent on post-transcriptional control, and therefore on the action of RBPs. These genetic features make trypanosomatids excellent models for the study of post-transcriptional regulation of gene expression. The roles of PRMTs in controlling the activity of RBPs in pathogenic kinetoplastids have now been studied for close to 2 decades with important advances achieved in recent years. These include the finding that about 10% of the Trypanosoma brucei proteome carries arginine methylation and that arginine methylation controls Leishmania:host interaction. Herein, we review how trypanosomatid PRMTs regulate the activity of RBPs, including by modulating interactions with RNA and/or protein complex formation, and discuss how this impacts cellular and biological processes. We further highlight unique structural features of trypanosomatid PRMTs and how it contributes to their singular functionality.



2020 ◽  
Vol 432 (23) ◽  
pp. 6061-6074
Author(s):  
Matthias Kracht ◽  
Johannes van den Boom ◽  
Jonas Seiler ◽  
Alexander Kröning ◽  
Farnusch Kaschani ◽  
...  


1998 ◽  
Vol 80 (4) ◽  
pp. 307-321
Author(s):  
John E. Hesketh ◽  
M. Helena Vasconcelos ◽  
Giovanna Bermano

Nutrition has marked influences on gene expression and an understanding of the interaction between nutrients and gene expression is important in order to provide a basis for determining the nutritional requirements on an individual basis. The effects of nutrition can be exerted at many stages between transcription of the genetic sequence and production of a functional protein. This review focuses on the role of post-transcriptional control, particularly mRNA stability, translation and localization, in the interactions of nutrients with gene expression. The effects of both macronutrients and micronutrients on regulation of gene expression by post-transcriptional mechanisms are presented and the post-transcriptional regulation of specific genes of nutritional relevance (glucose transporters, transferrin, selenoenzymes, metallothionein, lipoproteins) is described in detail. The function of the regulatory signals in the untranslated regions of the mRNA is highlighted in relation to control of mRNA stability, translation and localization and the importance of these mRNA regions to regulation by nutrients is illustrated by reference to specific examples. The localization of mRNA by signals in the untranslated regions and its function in the spatial organization of protein synthesis is described; the potential of such mechanisms to play a key part in nutrient channelling and metabolic compartmentation is discussed. It is concluded that nutrients can influence gene expression through control of the regulatory signals in these untranslated regions and that the post-transcriptional regulation of gene expression by these mechanisms may influence nutritional requirements. It is emphasized that in studies of nutritional control of gene expression it is important not to focus only on regulation through gene promoters but also to consider the possibility of post-transcriptional control.





1996 ◽  
Vol 325 (1) ◽  
pp. 82-90 ◽  
Author(s):  
Sumin Zhao ◽  
Wenle Xia ◽  
Ernest Y.C. Lee


Reproduction ◽  
2001 ◽  
pp. 41-48 ◽  
Author(s):  
CM Rodriguez ◽  
JL Kirby ◽  
BT Hinton

The epididymis exhibits region-specific as well as cell-specific patterns of gene expression within the epithelium. The spatial and temporal patterns of gene expression originate during development and are critical to the formation and maintenance of a fully functional epididymis. Despite the number of mechanisms reported to contribute to the regulation of eukaryotic gene expression, little is known about the specific mechanisms involved in the control of epididymal gene expression. This review will outline some of the cis-DNA elements and associated transcription factors that have been identified in the epididymis, in addition to discussing the potential role of co-regulator molecules and changes in chromatin structure as critical control points of gene expression. Although gene expression can be controlled at several points, discussion will focus on gene regulation at the transcriptional level. The role of post-transcriptional control, with particular attention to mRNA stability, will also be discussed.



1995 ◽  
Vol 32 (3) ◽  
pp. 167-175 ◽  
Author(s):  
Adrian M. Casillas ◽  
Andrew D. Thompson ◽  
Samuel Cheshier ◽  
Santiago Hernandez ◽  
Renato J. Aguilera


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