Abstract:
:Phosphorylation by protein kinases is a fundamental mechanism of signal transduction. Many kinase families contain one or several members that, although evolutionarily conserved, lack the residues required for catalytic activity. Studies combining structural, biochemical, and functional approaches revealed that these pseudokinases have crucial roles in vivo and may even represent attractive targets for pharmacological intervention. Pseudokinases mediate signal transduction by a diversity of mechanisms, including allosteric regulation of their active counterparts, assembly of signaling hubs, or modulation of protein localization. One such pseudokinase, named Tra1 in yeast and transformation/transcription domain-associated protein (TRRAP) in mammals, is the only member lacking all catalytic residues within the phosphatidylinositol 3-kinase related kinase (PIKK) family of kinases. PIKKs are related to the PI3K family of lipid kinases, but function as Serine/Threonine protein kinases and have pivotal roles in diverse processes such as DNA damage sensing and repair, metabolic control of cell growth, nonsense-mediated decay, or transcription initiation. Tra1/TRRAP is the largest subunit of two distinct transcriptional co-activator complexes, SAGA and NuA4/TIP60, which it recruits to promoters upon transcription factor binding. Here, we review our current knowledge on the Tra1/TRRAP pseudokinase, focusing on its role as a scaffold for SAGA and NuA4/TIP60 complex assembly and recruitment to chromatin. We further discuss its evolutionary history within the PIKK family and highlight recent findings that reveal the importance of molecular chaperones in pseudokinase folding, function, and conservation.
journal_name
Biochem Soc Transjournal_title
Biochemical Society transactionsauthors
Elías-Villalobos A,Fort P,Helmlinger Ddoi
10.1042/BST20180496subject
Has Abstractpub_date
2019-12-20 00:00:00pages
1597-1608issue
6eissn
0300-5127issn
1470-8752pii
221316journal_volume
47pub_type
杂志文章,评审abstract::The analysis of deep sequencing data allows for a genome-wide overview of all the small RNA molecules (the 'sRNome') that are present in a single organism. In the present paper, we review the processing of CRISPR (clustered regularly interspaced short palindromic repeats) RNA, C/D box sRNA (small non-coding RNA) and t...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20120276
更新日期:2013-02-01 00:00:00
abstract::The continuous battle for survival in the environment has led to the development or acquisition of sophisticated defence systems in bacteria. These defence systems have contributed to the survival of the bacterial species in the environment for millions of years. Some systems appear to have evolved in a number of path...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20130127
更新日期:2013-12-01 00:00:00
abstract::Zebrafish (Danio rerio) are becoming an increasingly powerful model organism to study the role of metabolism in disease. Since its inception, the zebrafish model has relied on unique attributes such as the transparency of embryos, high fecundity and conservation with higher vertebrates, to perform phenotype-driven che...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20180335
更新日期:2019-02-28 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders in industrialized countries. NAFLD develops in the absence of alcohol abuse and encompasses a wide spectrum of disorders ranging from benign fatty liver to non-alcoholic steatohepatitis (NASH). NASH often leads to fibrosis, cirrhosis a...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140138
更新日期:2014-10-01 00:00:00
abstract::The short consensus/complement repeat (SCR) domain (also known as the complement control protein domain) is the most abundant domain type in the complement system. Crystal and NMR structures for proteins that contain single and multiple SCR domains have now been published. These contain inter-SCR linkers of between th...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0300996
更新日期:2002-11-01 00:00:00
abstract::Protein-protein interactions are a regulatory mechanism for a number of physiological and pathological cellular processes. Neurodegenerative diseases, such as AD (Alzheimer's disease), are associated with the accelerated production or delayed clearance of protein aggregates. Hence, inhibition of pathologic protein-pro...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0330543
更新日期:2005-08-01 00:00:00
abstract::The ribosome is the macromolecular machinery in the host cell for which all viruses have to compete. Early in infection, the viral mRNAs have to compete with the host for both the ribosomes and for the limited pool of eukaryotic initiation factors that are needed to facilitate the recruitment of ribosomes to both vira...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20051479
更新日期:2005-12-01 00:00:00
abstract::Tribbles (TRIB) proteins are pseudokinase mediators of eukaryotic signalling that have evolved important roles in lipoprotein metabolism, immune function and cellular differentiation and proliferation. In addition, an evolutionary-conserved modulation of PI3K/AKT signalling pathways highlights them as novel and rather...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20150109
更新日期:2015-10-01 00:00:00
abstract::Many Zn(II)2Cys6 transcriptional regulators exhibit changes in phosphorylation that are coincident with their roles in transcriptional activation. It is, however, unclear whether these changes occur as a cause of, or as a result of, transcriptional activation. In this paper, we explore the relationship between these t...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0340794
更新日期:2006-11-01 00:00:00
abstract::For a disease such as cancer, where a number of alterations to normal cell function accumulate over time, there are several opportunities to inhibit, slow down or even reverse the process. Many of the changes which drive the disease process occur in cell-signalling pathways that regulate proliferation and apoptosis. A...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0280007
更新日期:2000-02-01 00:00:00
abstract::The function of biomolecules is intrinsically linked to their structure and the complexes they form during function. Techniques for the determination of structures and dynamics of these nanometre assemblies are therefore important for an understanding on the molecular level. PELDOR (pulsed electron-electron double res...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0390128
更新日期:2011-01-01 00:00:00
abstract::Signalling by pattern recognition receptors (PRRs) is critical for protecting the host against pathogens. Disruption of these signalling pathways has been implicated in many diseases ranging from infection susceptibility to cancer and autoimmune disease. Understanding how PRRs signal is of critical importance due to t...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20160459
更新日期:2017-10-15 00:00:00
abstract::NMDARs (N-methyl-D-aspartate receptors) are considered to be a target for the inhibitory actions of ethanol. While profound inhibition of both native and recombinant NMDARs can be observed following the application of high concentrations of ethanol the levels of inhibition seen with lower concentrations of ethanol are...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0371423
更新日期:2009-12-01 00:00:00
abstract::Copper chaperones, soluble copper-binding proteins, are essential for ensuring proper distribution of copper to cellular compartments and to proteins requiring copper prosthetic groups. They are found in all eukaryotic organisms. Orthologues of the three copper chaperones characterized in yeast, ATX1, CCS and COX17, a...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/bst0300732
更新日期:2002-08-01 00:00:00
abstract::The identification of nitric oxide-bound leghaemoglobin within soya bean nodules has led to the question of how Bradyrhizobium japonicum bacteroids overcome the toxicity of this nitric oxide. It has previously been shown that one candidate for nitric oxide detoxification, the respiratory nitric oxide reductase, is exp...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0340195
更新日期:2006-02-01 00:00:00
abstract::Human adipose tissue has an important protein secretory function. Cytokines, hormones, prohormones and enzymes are secreted from fat cells and act in an endocrine or paracrine fashion. The production of several of these proteins is affected by obesity; normally there is an increase in the obese state. Protein producti...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0290072
更新日期:2001-05-01 00:00:00
abstract::After years of setbacks, the perspective of neuroprotective stroke therapy has revived in light of recent study results. We outline in this review how a neuroprotective candidate drug should be developed, beginning with a thorough preclinical evaluation according to the STAIR (Stroke Therapy Academic Industry Roundtab...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0341271
更新日期:2006-12-01 00:00:00
abstract::African trypanosomes have plastic genomes with extensive variability at the chromosome ends. The genes encoding the expressed major surface protein of the infective bloodstream form stages of Trypanosoma brucei and are located at telomeres. These telomeric expression-site transcription units are turning out to be surp...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0280536
更新日期:2000-10-01 00:00:00
abstract::USP7 (also called HAUSP) is a de-ubiquitinating enzyme recently identified as a key regulator of the p53-mdm2 pathway, which stabilizes both p53 and mdm2. We have discovered that the Epstein-Barr nuclear antigen 1 protein of Epstein-Barr virus binds with high affinity to USP7 and disrupts the USP7-p53 interaction. The...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0320731
更新日期:2004-11-01 00:00:00
abstract::Inflammation or inflammatory cytokines and oxidative stress have often been associated, and thiol antioxidants, particularly glutathione, have often been seen as possible anti-inflammatory mediators. However, whereas several cytokine inhibitors have been approved for drug use in chronic inflammatory diseases, this has...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0391268
更新日期:2011-10-01 00:00:00
abstract::A considerable number of fungal homologues of human apoptotic genes have been identified in recent years. Nevertheless, we are far from being able to connect the different pieces and construct a primary structure of the fungal apoptotic regulatory network. To get a better picture of the available fungal components, we...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0391493
更新日期:2011-10-01 00:00:00
abstract::The recruitment of the furanosidic scaffold of ribose as the crucial step for nucleotides and then for nucleic acids synthesis is presented. Based on the view that the selection of molecules to be used for relevant metabolic purposes must favor structurally well-defined molecules, the inadequacy of ribose as a prefere...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20190749
更新日期:2019-12-20 00:00:00
abstract::Multiple cellular proteins have been identified as participating in Toll/interleukin-1 receptor-mediated inflammatory gene expression. The continuing isolation of novel components, based on sequence similarities, protein-protein interactions and protein purification, suggests that many elements of this signalling netw...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20051405
更新日期:2005-12-01 00:00:00
abstract::Frequent subversion of the PI3K (phosphoinositide 3-kinase) pathway during neoplastic transformation contributes to several hallmarks of cancer that result in a competitive advantage for cancer cells. Deregulation of this pathway can be the result of genomic alterations such as PIK3CA mutation, PTEN (phosphatase and t...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140034
更新日期:2014-08-01 00:00:00
abstract::A survey of archaeal genomes for the presence of homologues of bacterial and eukaryotic chaperones reveals several interesting features. All archaea contain chaperonins, also known as Hsp60s (where Hsp is heat-shock protein). These are more similar to the type II chaperonins found in the eukaryotic cytosol than to the...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0370046
更新日期:2009-02-01 00:00:00
abstract::Complex brains have developed specialized mechanisms for the grouping of principal cells into temporal coalitions of local or distant networks: the inhibitory interneuron 'clocking' networks. They consist of GABAergic (where GABA is gamma-aminobutyric acid) interneurons of a rich diversity. In cortical circuits, these...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0371328
更新日期:2009-12-01 00:00:00
abstract::The PI3K (phosphoinositide 3-kinase) family of lipid kinases regulate cell motility in diverse organisms and cell types. In mammals, the main PI3K enzyme activated by chemokine receptor signalling is the class IB isoform, p110gamma. Studies of p110gamma-knockout mice have shown an essential function for this isoform i...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0351109
更新日期:2007-11-01 00:00:00
abstract::Animal venoms are recognised as unique biological systems in which to study molecular evolution. Venom use has evolved numerous times among the insects, and insects today use venom to capture prey, defend themselves from predators, or to subdue and modulate host responses during parasitism. However, little is known ab...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20190820
更新日期:2020-08-28 00:00:00
abstract::Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-β (TGF-β) family signalling pathway. Similar to TGF-β, the complex roles of BMPs in development and disease are demonstrated by their dichotomous roles in various cancers and cancer stages. Although early studies implicated BMP signalling in t...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20160069
更新日期:2016-08-15 00:00:00
abstract::Membrane contact sites (MCSs) are subcellular regions where the membranes of distinct organelles come into close apposition. These specialized areas of the cell, which are involved in inter-organelle metabolite exchange, are scaffolded by specific complexes. STARD3 [StAR (steroidogenic acute regulatory protein)-relate...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20150269
更新日期:2016-04-15 00:00:00