Top

Published in:

Open Access 01-12-2021 | Short Communication

Targeted deletion of Ruvbl1 results in severe defects of epidermal development and perinatal mortality

Authors: Claudia Dafinger, Thomas Benzing, Jörg Dötsch, Bernhard Schermer, Max C. Liebau

Published in: Molecular and Cellular Pediatrics | Issue 1/2021

Abstract

Epidermal development is a complex process of regulated cellular proliferation, differentiation, and tightly controlled cell death involving multiple cellular signaling networks. Here, we report a first description linking the AAA+ (ATPases associated with various cellular activities) superfamily protein Ruvbl1 to mammalian epidermal development. Keratinocyte-specific Ruvbl1 knockout mice (Ruvbl1^fl/flK14:Cre^tg) show a severe phenotype including dramatic structural epidermal defects resulting in the loss of the functional skin barrier and perinatal death. Thus, Ruvbl1 is a newly identified essential player for the development of differentiated epidermis in mice.

Available only for authorised users

Hu MS, Borrelli MR, Hong WX, Malhotra S, Cheung ATM, Ransom RC et al (2018) Embryonic skin development and repair. Organogenesis 14(1):46–63CrossRef

Liu S, Zhang H, Duan E (2013) Epidermal development in mammals: key regulators, signals from beneath, and stem cells. Int J Mol Sci 14(6):10869–10895CrossRef

Abe Y, Tanaka N. Roles of the hedgehog signaling pathway in epidermal and hair follicle development, homeostasis, and cancer. J Dev Biol. 2017;5(4):12.

Koster MI, Roop DR (2007) Mechanisms regulating epithelial stratification. Annu Rev Cell Dev Biol. 23:93–113CrossRef

Nano N, Houry WA (2013) Chaperone-like activity of the AAA+ proteins Rvb1 and Rvb2 in the assembly of various complexes. Philos Trans R Soc Lond B Biol Sci 368(1617):20110399CrossRef

Grigoletto A, Lestienne P, Rosenbaum J (2011) The multifaceted proteins Reptin and Pontin as major players in cancer. Biochim Biophys Acta. 1815(2):147–157PubMed

Gallant P (2007) Control of transcription by Pontin and Reptin. Trends Cell Biol. 17(4):187–192CrossRef

Jha S, Dutta A (2009) RVB1/RVB2: running rings around molecular biology. Mol Cell 34(5):521–533CrossRef

Boulon S, Bertrand E, Pradet-Balade B (2012) HSP90 and the R2TP co-chaperone complex: building multi-protein machineries essential for cell growth and gene expression. RNA Biol. 9(2):148–154CrossRef

10.

Rosenbaum J, Baek SH, Dutta A, Houry WA, Huber O, Hupp TR et al (2013) The emergence of the conserved AAA+ ATPases Pontin and Reptin on the signaling landscape. Sci Signal 6(266):mr1CrossRef

11.

Kakihara Y, Saeki M (2014) The R2TP chaperone complex: its involvement in snoRNP assembly and tumorigenesis. Biomol Concepts. 5(6):513–520CrossRef

12.

Jha S, Shibata E, Dutta A (2008) Human Rvb1/Tip49 is required for the histone acetyltransferase activity of Tip60/NuA4 and for the downregulation of phosphorylation on H2AX after DNA damage. Mol Cell Biol. 28(8):2690–2700CrossRef

13.

Muñoz-Hernández H, Pal M, Rodríguez CF, Prodromou C, Pearl LH, Llorca O (2018) Advances on the structure of the R2TP/Prefoldin-like complex. Adv Exp Med Biol. 1106:73–83CrossRef

14.

Sykes SM, Mellert HS, Holbert MA, Li K, Marmorstein R, Lane WS et al (2006) Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Mol Cell 24(6):841–851CrossRef

15.

Dafinger C, Rinschen MM, Borgal L, Ehrenberg C, Basten SG, Franke M et al (2018) Targeted deletion of the AAA-ATPase Ruvbl1 in mice disrupts ciliary integrity and causes renal disease and hydrocephalus. Exp Mol Med 50(6):75CrossRef

16.

Bereshchenko O, Mancini E, Luciani L, Gambardella A, Riccardi C, Nerlov C (2012) Pontin is essential for murine hematopoietic stem cell survival. Haematologica. 97(9):1291–1294CrossRef

17.

Indra AK, Li M, Brocard J, Warot X, Bornert JM, Gérard C et al (2000) Targeted somatic mutagenesis in mouse epidermis. Horm Res. 54(5–6):296–300PubMed

18.

Kruiswijk F, Labuschagne CF, Vousden KH (2015) p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat Rev Mol Cell Biol. 16(7):393–405CrossRef

19.

Kaji K, Fertig N, Medsger TA, Satoh T, Hoshino K, Hamaguchi Y et al (2014) Autoantibodies to RuvBL1 and RuvBL2: a novel systemic sclerosis-related antibody associated with diffuse cutaneous and skeletal muscle involvement. Arthritis Care Res. 66(4):575–584CrossRef

20.

Nomura Y, Ueda-Hayakawa I, Yamazaki F, Ozaki Y, Hamaguchi Y, Takehara K et al (2020) A case of anti-RuvBL1/2 antibody-positive systemic sclerosis overlapping with myositis. Eur J Dermatol 30(1):52–53PubMed

Title: Targeted deletion of Ruvbl1 results in severe defects of epidermal development and perinatal mortality
Authors: Claudia Dafinger
Thomas Benzing
Jörg Dötsch
Bernhard Schermer
Max C. Liebau
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Published in: Molecular and Cellular Pediatrics / Issue 1/2021
Electronic ISSN: 2194-7791
DOI: https://doi.org/10.1186/s40348-021-00111-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Targeted deletion of Ruvbl1 results in severe defects of epidermal development and perinatal mortality

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2021

Aggressive infantile myofibromatosis with intestinal involvement

Does allogeneic stem cell transplantation in survivors of pediatric leukemia impact regular physical activity, pulmonary function, and exercise capacity?

Translational research approaches to study pediatric polycystic kidney disease

Relationship between adiponectin, TNFα, and SHBG in prepubertal children with obesity

Bacterial metabolites and cardiovascular risk in children with chronic kidney disease

Imaging of peripheral vascular malformations — current concepts and future perspectives