@article {624,
	title = {Ari-1 Regulates Myonuclear Organization Together with Parkin and Is Associated with Aortic Aneurysms.},
	journal = {Dev Cell},
	volume = {45},
	year = {2018},
	month = {2018 04 23},
	pages = {226-244.e8},
	abstract = {<p>Nuclei are actively positioned and anchored to the cytoskeleton via the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex. We identified mutations in the Parkin-like E3 ubiquitin ligase Ariadne-1 (Ari-1) that affect the localization and distribution of LINC~complex members in Drosophila. ari-1 mutants exhibit nuclear clustering and morphology defects in larval muscles. We show that Ari-1 mono-ubiquitinates the core LINC complex member Koi. Surprisingly, we discovered functional redundancy between Parkin and Ari-1: increasing Parkin expression rescues ari-1 mutant phenotypes and vice versa. We further show that rare variants in the human homolog of ari-1 (ARIH1) are associated with thoracic aortic aneurysms and dissections, conditions resulting from smooth muscle cell (SMC) dysfunction. Human ARIH1 rescues fly ari-1 mutant phenotypes, whereas human variants found in patients fail to do so. In addition, SMCs obtained from patients display aberrant nuclear morphology. Hence, ARIH1 is critical in anchoring myonuclei to the cytoskeleton.</p>},
	keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Animals, Aortic Aneurysm, Carrier Proteins, Cell Nucleus, Child, Preschool, Cytoskeleton, Drosophila melanogaster, Drosophila Proteins, Female, Humans, Male, Middle Aged, Mutation, Myocytes, Smooth Muscle, Pedigree, Phenotype, Ubiquitin-Protein Ligases, Young Adult},
	issn = {1878-1551},
	doi = {10.1016/j.devcel.2018.03.020},
	author = {Tan, Kai Li and Haelterman, Nele A and Kwartler, Callie S and Regalado, Ellen S and Lee, Pei-Tseng and Nagarkar-Jaiswal, Sonal and Guo, Dong-Chuan and Duraine, Lita and Wangler, Michael F and Bamshad, Michael J and Nickerson, Deborah A and Lin, Guang and Milewicz, Dianna M and Bellen, Hugo J}
}
@article {319,
	title = {Mutations in the TGF-β repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm.},
	journal = {Nat Genet},
	volume = {44},
	year = {2012},
	month = {2012 Nov},
	pages = {1249-54},
	abstract = {<p>Elevated transforming growth factor (TGF)-β signaling has been implicated in the pathogenesis of syndromic presentations of aortic aneurysm, including Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). However, the location and character of many of the causal mutations in LDS intuitively imply diminished TGF-β signaling. Taken together, these data have engendered controversy regarding the specific role of TGF-β in disease pathogenesis. Shprintzen-Goldberg syndrome (SGS) has considerable phenotypic overlap with MFS and LDS, including aortic aneurysm. We identified causative variation in ten individuals with SGS in the proto-oncogene SKI, a known repressor of TGF-β activity. Cultured dermal fibroblasts from affected individuals showed enhanced activation of TGF-β signaling cascades and higher expression of TGF-β-responsive genes relative to control cells. Morpholino-induced silencing of SKI paralogs in zebrafish recapitulated abnormalities seen in humans with SGS. These data support the conclusions that increased TGF-β signaling is the mechanism underlying SGS and that high signaling contributes to multiple syndromic presentations of aortic aneurysm.</p>},
	keywords = {Animals, Aortic Aneurysm, Arachnodactyly, Cells, Cultured, Craniosynostoses, DNA-Binding Proteins, Fibroblasts, Humans, Loeys-Dietz Syndrome, Marfan Syndrome, Mice, Mutation, Phenotype, Phosphorylation, Proto-Oncogene Proteins, Signal Transduction, Transforming Growth Factor beta, Zebrafish},
	issn = {1546-1718},
	doi = {10.1038/ng.2421},
	author = {Doyle, Alexander J and Doyle, Jefferson J and Bessling, Seneca L and Maragh, Samantha and Lindsay, Mark E and Schepers, Dorien and Gillis, Elisabeth and Mortier, Geert and Homfray, Tessa and Sauls, Kimberly and Norris, Russell A and Huso, Nicholas D and Leahy, Dan and Mohr, David W and Caulfield, Mark J and Scott, Alan F and Destr{\'e}e, Anne and Hennekam, Raoul C and Arn, Pamela H and Curry, Cynthia J and Van Laer, Lut and McCallion, Andrew S and Loeys, Bart L and Dietz, Harry C}
}
