2019
DOI: 10.1042/bst20180496
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New insights into the evolutionary conservation of the sole PIKK pseudokinase Tra1/TRRAP

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, includi… Show more

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Cited by 28 publications
(36 citation statements)
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“…Family members of phosphatidylinositol 3-kinase-related kinases (PIKKs) activate distinct signaling pathways that promote cellular survival in different environmental and endogenous stress conditions ( Baretić and Williams, 2014 ; Imseng et al, 2018 ; Lempiäinen and Halazonetis, 2009 ). Specifically, PIKKs oversee translation machinery in the cytoplasm (mTOR, SMG1), or regulate DNA damage repair in the nucleus (ATM, ATR and DNA-PK) ( Shimobayashi and Hall, 2014 ; Saxton and Sabatini, 2017 ; Yamashita, 2013 ; Yamashita et al, 2001 ; Blackford and Jackson, 2017 ; Elías-Villalobos et al, 2019 ). With the exception of the enzymatically inactive TRAPP/Tra1, which serves as a scaffold in chromatin modification complexes, all other members of the PIKK family are Ser/Thr-protein kinases, and are among the largest proteins in the eukaryotic kinome.…”
Section: Introductionmentioning
confidence: 99%
“…Family members of phosphatidylinositol 3-kinase-related kinases (PIKKs) activate distinct signaling pathways that promote cellular survival in different environmental and endogenous stress conditions ( Baretić and Williams, 2014 ; Imseng et al, 2018 ; Lempiäinen and Halazonetis, 2009 ). Specifically, PIKKs oversee translation machinery in the cytoplasm (mTOR, SMG1), or regulate DNA damage repair in the nucleus (ATM, ATR and DNA-PK) ( Shimobayashi and Hall, 2014 ; Saxton and Sabatini, 2017 ; Yamashita, 2013 ; Yamashita et al, 2001 ; Blackford and Jackson, 2017 ; Elías-Villalobos et al, 2019 ). With the exception of the enzymatically inactive TRAPP/Tra1, which serves as a scaffold in chromatin modification complexes, all other members of the PIKK family are Ser/Thr-protein kinases, and are among the largest proteins in the eukaryotic kinome.…”
Section: Introductionmentioning
confidence: 99%
“…TRRAP regulates transcription as part of either the TIP60 or the SAGA co-activator complex (30). We thus asked whether SAGA and TIP60 contribute to ISG repression in HCT116 cells.…”
Section: Both Tip60 and Saga Contribute To Isg Repressionmentioning
confidence: 99%
“…TRRAP is an evolutionary conserved member of an atypical family of kinases, called phosphoinositide 3 kinase-related kinases (PIKK), with which it shares a characteristic domain architecture. However, TRRAP lacks all catalytic residues and is therefore the sole pseudokinase of this family (reviewed in (30)). Active PIKKs are implicated in diverse processes.…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…Tra1/TRRAP is an essential component of SAGA and NuA4 complexes (35)(36)(37). It is a member of the PIKK (phosphoinositide-3-kinase-related kinase) family that also includes Tor1, ATM and Rad3-related protein (ATR/Mec1), and the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) (38).…”
Section: Introductionmentioning
confidence: 99%