FAT: a novel domain in PIK-related kinases

Bosotti, Roberta; Isacchi, Antonella; Sonnhammer, Erik L. L.

doi:10.1016/s0968-0004(00)01563-2

Cited by 266 publications

(209 citation statements)

References 22 publications

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“…In mice expressing this mutant Nbs1, there was a defect in DNA damage-induced intra-S checkpoint activation in mouse (Bakkenist and Kastan, 2003;Kozlov et al, 2006). The identified domains within ATM consist of the nuclear localization signal (NLS) , the leucine zipper (LZ) (Savitsky et al, 1995b), the FRAP/ATM/TRRAP (FAT) domain (Bosotti et al, 2000), the Kinase domain (PI3-K) (Savitsky et al, 1995a), and the FAT c-terminal (FATC) domain (Bosotti et al, 2000). (b) Nbs1 is a 90 kDa protein, consisting of 754 amino acids.…”

Section: Role Of the C-terminus Of Nbs1mentioning

confidence: 99%

Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

2007

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The ataxia-telangiectasia-mutated (ATM) protein kinase is rapidly and specifically activated in response to DNA double-strand breaks in eukaryotic cells. In this review, we summarize recent insights into the mechanism of ATM activation, focusing on the role of the Mre11/Rad50/Nbs1 (MRN) complex in this process. We also compare observations of the ATM activation process in different biological systems and highlight potential candidates for cellular factors that may participate in regulating ATM activity in human cells.

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Section: Role Of the C-terminus Of Nbs1mentioning

confidence: 99%

Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

2007

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“…This PI3-kinase-like domain is flanked by two loosely conserved stretches of amino acids termed FAT (FRAP, ATM and TRRAP) domain that spans approximately 500 amino acids and FATC (FRAP, ATM and TRRAP, C terminus) domain of only 35 amino acids at the extreme C terminus (Bosotti et al, 2000;Shiloh, 2003;Abraham, 2004). The exact function of the FAT domain remains unclear, whereas the FATC domain appears to be critical for the kinase activity of the proteins of the PIKK family.…”

Section: Trrap Is Conserved In Evolutionmentioning

confidence: 99%

Orchestration of chromatin-based processes: mind the TRRAP

et al. 2007

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Chromatin modifications at core histones including acetylation, methylation, phosphorylation and ubiquitination play an important role in diverse biological processes. Acetylation of specific lysine residues within the N terminus tails of core histones is arguably the most studied histone modification; however, its precise roles in different cellular processes and how it is disrupted in human diseases remain poorly understood. In the last decade, a number of histone acetyltransferases (HATs) enzymes responsible for histone acetylation, has been identified and functional studies have begun to unravel their biological functions. The activity of many HATs is dependent on HAT complexes, the multiprotein assemblies that contain one HAT catalytic subunit, adapter proteins, several other molecules of unknown function and a large protein called TRansformation/tRanscription domain-Associated Protein (TRRAP). As a common component of many HAT complexes, TRRAP appears to be responsible for the recruitment of these complexes to chromatin during transcription, replication and DNA repair. Recent studies have shed new light on the role of TRRAP in HAT complexes as well as mechanisms by which it mediates diverse cellular processes. Thus, TRRAP appears to be responsible for a concerted and context-dependent recruitment of HATs and coordination of distinct chromatin-based processes, suggesting that its deregulation may contribute to diseases. In this review, we summarize recent developments in our understanding of the function of TRRAP and TRRAP-containing HAT complexes in normal cellular processes and speculate on the mechanism underlying abnormal events that may lead to human diseases such as cancer.

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“…These proteins are characterized by a domain similar to that in phosphatidylinositol 3-kinase and most PIKKs, including ATM, are active serine/ threonine kinases. ATM also contains a C-terminal FAT domain (FRAP, ATM, TRAPP), with a highly conserved 35 residue tail known as the FATC domain (Bosotti et al, 2000). This domain appears to be important for regulating the kinase activity of ATM and for binding regulatory proteins (Jiang et al, 2006).…”

Section: Atm Structure and Functionmentioning

confidence: 99%

ATM and breast cancer susceptibility

2006

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ATM was originally identified by positional cloning as the gene that underlies the autosomal recessive condition ataxia-telangiectasia. The encoded protein plays a central role in the complex processes that repair DNA doublestrand breaks. Nearly 20 years ago, epidemiological surveys of relatives of ataxia-telangiectasia cases suggested that female relatives were at modestly increased risk of breast cancer. Subsequently, many studies have tried to clarify the role of ATM in breast cancer susceptibility, but have produced inconclusive and/or inconsistent results. Recently, large epidemiological and molecular studies have finally provided conclusive evidence that ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles.

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FAT: a novel domain in PIK-related kinases

Cited by 266 publications

References 22 publications

Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

Orchestration of chromatin-based processes: mind the TRRAP

ATM and breast cancer susceptibility

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