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Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16
by
Brooke, Matthew A.
, Moncada-Pazos, Angela
, Maruthappu, Thiviyani
, Delaney, Paul J.
, Blaydon, Diana
, Kelsell, David P.
, Fell, Benjamin
, Waseem, Ahmad
, Freeman, Matthew
, Leigh, Irene M.
, Chikh, Anissa
, Ishida-Yamamoto, Akemi
, Levet, Clemence
in
13/1
/ 13/106
/ 13/109
/ 13/21
/ 13/44
/ 13/51
/ 13/89
/ 13/95
/ 14/19
/ 14/63
/ 38/111
/ 38/70
/ 38/77
/ 631/136/2091
/ 631/80/128/1580
/ 692/699/1503/1476/1477
/ 82
/ 82/29
/ 96
/ Animals
/ Carrier Proteins - genetics
/ Carrier Proteins - metabolism
/ Cell Line
/ Cell Proliferation - physiology
/ Cytoskeleton - physiology
/ Dentistry
/ Down-Regulation
/ Epidermal Cells
/ Epidermis
/ Epidermis - physiology
/ Esophageal cancer
/ Esophageal Neoplasms - genetics
/ Esophageal Neoplasms - pathology
/ Female
/ Fibroblasts
/ Gain of Function Mutation
/ Humanities and Social Sciences
/ Humans
/ Intracellular Signaling Peptides and Proteins
/ Keratin
/ Keratin-16 - metabolism
/ Keratin-6 - metabolism
/ Keratinocytes - physiology
/ Keratoderma, Palmoplantar - genetics
/ Keratoderma, Palmoplantar - pathology
/ Male
/ Mice
/ Mice, Knockout
/ multidisciplinary
/ Mutation
/ Physiology
/ Pressure
/ RNA, Small Interfering - metabolism
/ Science
/ Science (multidisciplinary)
/ Stress, Physiological - physiology
/ Tissue Culture Techniques
/ Up-Regulation
/ Wound healing
/ Wound Healing - physiology
2017
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Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16
by
Brooke, Matthew A.
, Moncada-Pazos, Angela
, Maruthappu, Thiviyani
, Delaney, Paul J.
, Blaydon, Diana
, Kelsell, David P.
, Fell, Benjamin
, Waseem, Ahmad
, Freeman, Matthew
, Leigh, Irene M.
, Chikh, Anissa
, Ishida-Yamamoto, Akemi
, Levet, Clemence
in
13/1
/ 13/106
/ 13/109
/ 13/21
/ 13/44
/ 13/51
/ 13/89
/ 13/95
/ 14/19
/ 14/63
/ 38/111
/ 38/70
/ 38/77
/ 631/136/2091
/ 631/80/128/1580
/ 692/699/1503/1476/1477
/ 82
/ 82/29
/ 96
/ Animals
/ Carrier Proteins - genetics
/ Carrier Proteins - metabolism
/ Cell Line
/ Cell Proliferation - physiology
/ Cytoskeleton - physiology
/ Dentistry
/ Down-Regulation
/ Epidermal Cells
/ Epidermis
/ Epidermis - physiology
/ Esophageal cancer
/ Esophageal Neoplasms - genetics
/ Esophageal Neoplasms - pathology
/ Female
/ Fibroblasts
/ Gain of Function Mutation
/ Humanities and Social Sciences
/ Humans
/ Intracellular Signaling Peptides and Proteins
/ Keratin
/ Keratin-16 - metabolism
/ Keratin-6 - metabolism
/ Keratinocytes - physiology
/ Keratoderma, Palmoplantar - genetics
/ Keratoderma, Palmoplantar - pathology
/ Male
/ Mice
/ Mice, Knockout
/ multidisciplinary
/ Mutation
/ Physiology
/ Pressure
/ RNA, Small Interfering - metabolism
/ Science
/ Science (multidisciplinary)
/ Stress, Physiological - physiology
/ Tissue Culture Techniques
/ Up-Regulation
/ Wound healing
/ Wound Healing - physiology
2017
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Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16
by
Brooke, Matthew A.
, Moncada-Pazos, Angela
, Maruthappu, Thiviyani
, Delaney, Paul J.
, Blaydon, Diana
, Kelsell, David P.
, Fell, Benjamin
, Waseem, Ahmad
, Freeman, Matthew
, Leigh, Irene M.
, Chikh, Anissa
, Ishida-Yamamoto, Akemi
, Levet, Clemence
in
13/1
/ 13/106
/ 13/109
/ 13/21
/ 13/44
/ 13/51
/ 13/89
/ 13/95
/ 14/19
/ 14/63
/ 38/111
/ 38/70
/ 38/77
/ 631/136/2091
/ 631/80/128/1580
/ 692/699/1503/1476/1477
/ 82
/ 82/29
/ 96
/ Animals
/ Carrier Proteins - genetics
/ Carrier Proteins - metabolism
/ Cell Line
/ Cell Proliferation - physiology
/ Cytoskeleton - physiology
/ Dentistry
/ Down-Regulation
/ Epidermal Cells
/ Epidermis
/ Epidermis - physiology
/ Esophageal cancer
/ Esophageal Neoplasms - genetics
/ Esophageal Neoplasms - pathology
/ Female
/ Fibroblasts
/ Gain of Function Mutation
/ Humanities and Social Sciences
/ Humans
/ Intracellular Signaling Peptides and Proteins
/ Keratin
/ Keratin-16 - metabolism
/ Keratin-6 - metabolism
/ Keratinocytes - physiology
/ Keratoderma, Palmoplantar - genetics
/ Keratoderma, Palmoplantar - pathology
/ Male
/ Mice
/ Mice, Knockout
/ multidisciplinary
/ Mutation
/ Physiology
/ Pressure
/ RNA, Small Interfering - metabolism
/ Science
/ Science (multidisciplinary)
/ Stress, Physiological - physiology
/ Tissue Culture Techniques
/ Up-Regulation
/ Wound healing
/ Wound Healing - physiology
2017
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Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16
Journal Article
Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16
2017
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Overview
Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of
irhom2
−/−
mice compared with
irhom2
+/+
mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this ‘stress’ keratin is regulated.
Keratin 16 is an epithelial protein highly expressed at pressure bearing sites and during wound healing and cancer. Here the authors show that K16 interacts with the inactive protease Rhbdf2, associated with Tylosis with oesophageal cancer, and that this interaction drives increased keratinocyte proliferation.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/109
/ 13/21
/ 13/44
/ 13/51
/ 13/89
/ 13/95
/ 14/19
/ 14/63
/ 38/111
/ 38/70
/ 38/77
/ 82
/ 82/29
/ 96
/ Animals
/ Carrier Proteins - metabolism
/ Cell Proliferation - physiology
/ Esophageal Neoplasms - genetics
/ Esophageal Neoplasms - pathology
/ Female
/ Humanities and Social Sciences
/ Humans
/ Intracellular Signaling Peptides and Proteins
/ Keratin
/ Keratoderma, Palmoplantar - genetics
/ Keratoderma, Palmoplantar - pathology
/ Male
/ Mice
/ Mutation
/ Pressure
/ RNA, Small Interfering - metabolism
/ Science
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