Molecular basis for the effect of the L31F mutation on <scp>CARD</scp> function in <scp>ARC</scp>

Ha, Hyekyung; Park, Hyun Ho

doi:10.1002/1873-3468.12783

Cited by 4 publications

(4 citation statements)

References 30 publications

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“…F164 is located in the helix bundle and forms a hydrophobic cluster with neighboring hydrophobic residues (L127, V135, and L180), which could be critical for maintaining the stability of six-helix bundle fold of the DD ( Fig 1D ). A previous study showed that CARD, another member of the DDS, is critical for interactions in the hydrophobic cluster, which in turn maintains the stability of the fold [ 38 ]. R170 is located in the type I interface, which is formed via interactions among the H4 of the first DD and H5-H6 loop and the H6 helix of the second DD ( Fig 1D ).…”

Section: Resultsmentioning

confidence: 99%

RAIDD mutations underlie the pathogenesis of thin lissencephaly (TLIS)

Park

2018

PLoS ONE

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Abnormal regulation of caspase-2-mediated neuronal cell death causes neurodegenerative diseases and defective brain development. PIDDosome is caspase-2 activating complex composed of PIDD, RAIDD, and caspase-2. Recent whole-exome sequencing study showed that the RAIDD mutations in the death domain (DD), including G128R, F164C, R170C, and R170H mutations, cause thin lissencephaly (TLIS) by reducing caspase-2-mediated neuronal apoptosis. Given that the molecular structure of the RAIDD DD:PIDD DD complex is available, in this study, we analyzed the molecular mechanisms underlying TLIS caused by the RAIDD TLIS variants by performing mutagenesis and biochemical assays.

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Section: Resultsmentioning

confidence: 99%

RAIDD mutations underlie the pathogenesis of thin lissencephaly (TLIS)

Park

2018

PLoS ONE

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“…The ARC CARD contains a 5-helix bundle fold (H1-H5) instead of a 6-helix bundle (Fig. 1C and D) (42,61), with helix H6 being disordered and not present in the structure. This indicates that H6 in the CARD is not necessary for its function, and even for the function of the DD super-family (Fig.…”

Section: Structure Of Cardsmentioning

confidence: 99%

“…Several apoptosis inhibitors, including apoptosis repressor with CARD (ARC), also contain CARDs (40,41). ARC may inhibit death-inducing signaling complex assembly followed by caspase activation by binding to the Fas-associated protein with DD (FADD) DD, Fas DD and caspase-8 DED using its CARD (42-44). This protein also inhibits p53 tetramerization and the function of p53 (45).…”

Section: Introductionmentioning

confidence: 99%

Caspase recruitment domains for protein�interactions in cellular signaling (Review)

Park

2019

Int J Mol Med

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The caspase recruitment domain (CARD), a well-known protein interaction module, belongs to the death domain (DD) superfamily, which includes DDs, death effector domains, and pyrin domains. The DD superfamily mediates the protein interactions necessary for apoptosis and immune cell signaling pathways. Among these domains, the CARD has been studied extensively as it mediates important cellular signaling events that are associated with various human diseases including cancer, neuro-degenerative diseases and immune disorders. Homo-type and hetero-type CARD-CARD interactions mediate the formation of large signaling complexes, including caspase-activating complexes and downstream signaling complexes. The present review summarizes and discusses the results of structural studies of various CARDs and their complexes. These studies shed light on the mechanisms that control the assembly and disassembly of signaling complexes and provide an improved understanding of cellular signaling processes.

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“…ARC antagonizes the intrinsic pathway by interacting with apoptosis-associated proteins (11). The binding of ARC and Bax, which can inhibit Bax activation and accumulation in the mitochondria (15), increases the Bcl2 apoptosis regulator/Bax ratio (71,72), stabilizes the mitochondrial membrane and prevents cytochrome c release (27,73,74). Furthermore, ARC is also involved in the regulation of mitochondrial dynamics.…”

Section: Cytoprotection and Anti-apoptosis Mechanisms Of Arcmentioning

confidence: 99%

Role of apoptosis repressor with caspase recruitment domain (arc) in cancer (Review)

et al. 2019

Oncol Lett

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Apoptosis repressor with caspase recruitment domain (ARC) is a potent inhibitor of apoptosis. Under physiological conditions, ARC is abundantly expressed in terminally differentiated cells, including cardiomyocytes, skeletal muscles and neurons. ARC serves a key role in determining cell fate, and abnormal ARC expression has been demonstrated to be associated with abnormal cell growth. Previous studies have revealed that ARC was upregulated in several different types of solid tumor, where it suppressed tumor cell apoptosis. Furthermore, the increased expression levels of ARC in cancer cells contributed to the development of therapeutic resistance and adverse clinical outcomes in patients with leukemia. However, the exact role of ARC, as well as the underlying molecular mechanisms involved, remain poorly understood. The present review summarizes the characteristics of ARC and its cytoprotective role under different conditions and describes the potential ARC as a new target for cancer therapy.

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Molecular basis for the effect of the L31F mutation on CARD function in ARC

Cited by 4 publications

References 30 publications

RAIDD mutations underlie the pathogenesis of thin lissencephaly (TLIS)

RAIDD mutations underlie the pathogenesis of thin lissencephaly (TLIS)

Caspase recruitment domains for protein�interactions in cellular signaling (Review)

Role of apoptosis repressor with caspase recruitment domain (arc) in cancer (Review)

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