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Study identified iRHOM2 as a novel regulator of K16 in humans and mice, with important implications for palmoplantar keratodermas, wound healing, inflammatory skin disease and cancers.
Uev1A-Ubc13 complex catalyzes lysine63-linked ubiquitination of RHBDF2 to promote TACE maturation.
In the late phase of RNA viral infection, iRhom2 mediates proteasome-dependent degradation of the E3 ubiquitin ligase MARCH5 and impairs mitochondria-associated degradation (MAD) of VISA.
The iRhom2 N-terminus stabilizes mature ADAM17 at the cell surface where it cleaves TNF and EGFR in inflammatory and innate immune responses. (Review)
results explain how loss of the amino terminus in iRhom1 and iRhom2 impairs TNF signaling, despite enhancing ADAM17 activity
Tylosis with oesophageal cancer-associated mutations in iRHOM2 cause an increase in the maturation and activity of ADAM17 in epidermal keratinocytes.
Our analyses suggest that these DNA methylation changes may have a role in the onset of Alzheimer disease given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known susceptibility gene network.
Identification of a new missense mutation, p.Asp188Asn, segregating with tylosis with esophageal cancer in a Finnish family, and interestingly the detected mutation alters a codon located between the two previously reported mutation sites.
RHBDF2 and CYGB may play distinctive roles in ovarian cancer and could be added to the growing roster of chromosome 17 genes implicated in this disease.
The distribution of RHBDF2 in tylotic skin is altered in comparison with that in normal skin.
These findings indicated that iRhom2 played an essential role in regulating particulate matter (PM2.5) -induced chronic renal damage, thus revealing a potential target for preventing chronic kidney diseases development.
iRHOM2 is a novel target gene of p63 and that both p63 and iRHOM2 differentially regulate cellular stress-associated signalling pathways in normal and hyperproliferative keratinocytes.
A tissue-specifc function of RHBDF2 rather than the surrounding microenvironment or the immune system underlies hyperproliferative skin disease.
iRhom2 controls multiple aspects of TACE biology, including stimulated shedding on the cell surface.
Overall, iRhom2 binds to TACE throughout its lifecycle, implying that iRhom2 is a primary regulator of stimulated cytokine and growth factor signalling.
long-term PM2.5 exposure caused hepatic steatosis and dyslipidemia through triggering inflammation, which was, at least partly, dependent on iRhom2/TNF-alpha pathway in liver-resident macrophages
baseline expression of genes acting within the NRF2 anti-oxidative pathway, followed by gene alterations associated with the integrin receptor aggregation pathway and the FcgammaR-mediated phagocytosis pathway, contribute to accelerated wound healing
the critical role of the transmembrane domains of ADAM17 and Rhbdf2 in the regulation of the ADAM17 and EGFR, and ADAM17 and TNFalpha signaling pathways, was examined.
this study shows that the iRhom2/ADAM17 pathway plays an important role in regulating CSF1R expression in the myeloid cell compartment at steady state, and in modulating development of monocytes/macrophages during their repopulation
this study shows that iRhom2-deficient mice were more susceptible to lethal herpes simplex virus type 1 infection, and that iRhom2 is essential for STING activity, as it regulates TRAPbeta-mediated translocation and EIF3S5-mediated deubiquitination of STING
This study identifies iRhom2 as a novel regulator for determination of keratinocyte lineages.
IRhom2 may be a promising therapeutic target for LPS-induced cardiac injury.
iRhom2 is required for the maturation of TACE and hair follicle differentiation.
a principal function of iRhoms1/2 during mouse development is to regulate ADAM17-dependent EGFR signaling
Rhbdf2 mutations increase its protein stability and drive EGFR hyperactivation through enhanced secretion of amphiregulin.
findings uncover functions for iRhom2 in the regulation of EGFR signaling and in controlling the activation and substrate selectivity of ADAM17-dependent shedding events
mice lacking Rhbdf2 were protected from K/BxN inflammatory arthritis to the same extent as mice lacking TACE in myeloid cells or Tnfa-deficient mice
These results establish a specific role for iRhom2 in the secretion of TNFalpha.
iRhom2 is required for TNF release; iRhom2 binds TACE and promotes its exit from the ER; failure of TACE to exit the ER in the absence of iRhom2 prevents the furin-mediated maturation and trafficking of TACE to the cell surface, the site of TNF cleavage
Rhomboid protease-like protein which has no protease activity but regulates the secretion of several ligands of the epidermal growth factor receptor. Indirectly activates the epidermal growth factor receptor signaling pathway and may thereby regulate sleep, cell survival, proliferation and migration (By similarity).
, inactive rhomboid protein 2
, rhomboid family member 2
, rhomboid veinlet-like protein 5
, rhomboid veinlet-like protein 6
, rhomboid, veinlet-like 6
, rhomboid-like protein 6
, rhomboid-related protein
, Rhomboid family member 2
, rhomboid veinlet-like 6