2023
DOI: 10.1242/jcs.260910
|View full text |Cite
|
Sign up to set email alerts
|

Analysis of the function of ADAM17 in iRhom2 curly-bare and tylosis with esophageal cancer mutant mice

Abstract: Tylosis with Oesophageal Cancer (TOC), is a rare familial disorder caused by cytoplasmic mutations in inactive rhomboid 2 (iR2). iR2 and the related iR1 are key regulators of the membrane-anchored metalloprotease ADAM17, which is required for activating EGFR ligands and for releasing pro-inflammatory cytokines such as TNFa. A cytoplasmic deletion in iR2, including the TOC site, leads to curly whiskers and bare skin (cub) in mice, whereas a knock-in TOC mutation causes less severe alopecia and wavy fur. The abn… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
2

Citation Types

6
5
0

Year Published

2023
2023
2024
2024

Publication Types

Select...
3
1

Relationship

1
3

Authors

Journals

citations
Cited by 4 publications
(11 citation statements)
references
References 63 publications
6
5
0
Order By: Relevance
“…Our findings that cub and TOC mutations decreases levels of mature ADAM17 is in line with recent in vivo and ex vivo results (Siggs et al, 2014, Rabinowitsch et al, 2023). However, these findings are counterintuitive to the earlier reported elevated ADAM17 shedding activity (Brooke et al, 2014, Hosur et al, 2017, Hosur et al, 2018a, Hosur et al, 2018b).…”
Section: Resultssupporting
confidence: 93%
See 2 more Smart Citations
“…Our findings that cub and TOC mutations decreases levels of mature ADAM17 is in line with recent in vivo and ex vivo results (Siggs et al, 2014, Rabinowitsch et al, 2023). However, these findings are counterintuitive to the earlier reported elevated ADAM17 shedding activity (Brooke et al, 2014, Hosur et al, 2017, Hosur et al, 2018a, Hosur et al, 2018b).…”
Section: Resultssupporting
confidence: 93%
“…The N-terminus of iRhoms emerges as a critical determinant for the stability and activity of the iRhom-ADAM17 complex. This is again supported by our data and was recently also confirmed in vivo : mice with the cub mutation show decreased ADAM17 levels in different tissues (Rabinowitsch et al, 2023). Recent findings highlight the significance of FRMD8-binding in regulating iRhom stability and, consequently, ADAM17 stability and functions (Künzel et al, 2018, Oikonomidi et al, 2018).…”
Section: Discussionsupporting
confidence: 91%
See 1 more Smart Citation
“…Our findings that cub and TOC mutations decrease levels of matured ADAM17 are in line with recent in vivo and ex vivo results [ 84 , 100 ]. However, these findings are counterintuitive to the earlier reported elevated ADAM17 shedding activity [ 14 , 39 , 40 , 42 ].…”
Section: Resultssupporting
confidence: 93%
“…In contrast, expression of the murine iRhom2 cub deletion does not promote higher levels of matured ADAM17 (Fig. 3 A), which is in line with recent in vivo findings [ 84 ]. Furthermore, the three deletions nd197, nd349 and nd370 showed also a significant decrease in matured ADAM17 levels compared to wt-iRhom2 (Fig.…”
Section: Resultssupporting
confidence: 91%