Human Hairless Protein Roles in Skin and Hair and Emerging Connections to Brain and Other Cancers

May 2017 in “ Journal of Cellular Biochemistry ”

Anas Maatough, G. Kerr Whitfield, Lemlem Brook, David Hsieh, Patricia Palade, Jui Cheng Hsieh, Anas Maatough, G. Kerr Whitfield, Lemlem Brook, David Hsieh, Patricia Palade, Jui Cheng Hsieh

hairless protein HR nuclear transcription factor hair cycling skin maintenance DNA binding histone demethylation nuclear translocation protein interactions nuclear receptors vitamin D thyroid hormone HR mutations alopecia histone H3K9 demethylase p53

Studysummary This review discusses the role of the hairless protein (HR) in alopecia and cancer, noting its potential importance in cancer cell growth and survival, and reports no new experimental results.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

The study explored the roles of the mammalian hairless protein (HR), a 130 kDa nuclear transcription factor, in skin and hair follicle function, as well as its expression in the brain and other tissues. HR was found to interact with nuclear receptors for vitamin D and thyroid hormone, potentially influencing DNA binding, histone demethylation, and protein interactions. Nearly 200 HR mutations were identified in various cancers, suggesting a role in cancer cell growth and survival. The study highlighted HR's potential involvement in carcinogenesis through histone demethylase activity and interactions with p53 pathways. The review summarized HR's bioactions, its mutations' contributions to alopecia and cancer, and proposed future research directions.

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Research cited in this study

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research The Mammalian Hairless Protein as a DNA Binding Phosphoprotein

6 citations , June 2016 in “Journal of cellular biochemistry”

This study found that the mammalian Hr protein can interact with the p53 pathway by binding to a specific p53 response element, influencing the regulation of genes involved in cell cycle control.

research Hairless Up-Regulates TGF-β2 Expression via Down-Regulation of miR-31 in the Skin of Hairpoor (HrHp) Mice

11 citations , January 2015 in “Journal of cellular physiology”

This study suggests that abnormal hair cycles in Hr mutant mice may be caused by HR protein overexpression, which down-regulates miR-31 and increases Tgf-β2 expression.

research Hairless Plays a Role in Formation of Inner Root Sheath via Regulation of Dlx3 Gene

17 citations , March 2012 in “Journal of biological chemistry/The Journal of biological chemistry”

In this study, researchers found that overexpression of the hairless protein in Hr mutant mice disrupts inner root sheath formation by downregulating Dlx3 and associated keratins in hair follicle development.

research Analysis of Hairless Corepressor Mutants to Characterize Molecular Cooperation with the Vitamin D Receptor in Promoting the Mammalian Hair Cycle

22 citations , April 2010 in “Journal of Cellular Biochemistry”

This study concluded that the hairless protein interacts with the vitamin D receptor to repress transcription crucial for hair cycling, employing multiple protein interfaces and modulating chromatin structure.

Loss-Of-Function Mutations of an Inhibitory Upstream ORF in the Human Hairless Transcript Cause Marie Unna Hereditary Hypotrichosis

research Loss-Of-Function Mutations of an Inhibitory Upstream ORF in the Human Hairless Transcript Cause Marie Unna Hereditary Hypotrichosis

181 citations , January 2009 in “Nature Genetics”

In this study, researchers linked defects in U2HR, an inhibitory region in the HR gene, to Marie Unna hereditary hypotrichosis, suggesting a mechanism for controlling hair growth and addressing hair loss.

research The Near-Naked Hairless Mutation Disrupts Hair Formation but Is Not Due to a Mutation in the Hairless Coding Region

8 citations , March 2007 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study reports that the near-naked hairless mutation in mice is not an allele of the Hairless gene but may involve a mutation in a linked gene or a regulatory mutation.

research Hairless and Wnt Signaling: Allies in Epithelial Stem Cell Differentiation

74 citations , September 2006 in “Cell Cycle”

This review examines the role of Hairless, a nuclear receptor corepressor, in regulating Wnt signaling during hair cycling and reports no new clinical results.

research Physical And Functional Interaction Between The Vitamin D Receptor And Hairless Corepressor, Two Proteins Required For Hair Cycling

215 citations , September 2003 in “Journal of Biological Chemistry”

This study found that the hairless gene product (Hr) suppresses VDR-mediated gene activation by directly interacting with the vitamin D receptor, potentially affecting hair follicle function.

research The Hairless Gene Mutated in Congenital Hair Loss Disorders Encodes a Novel Nuclear Receptor Corepressor

178 citations , October 2001 in “Genes & Development”

This study found that the mammalian hairless gene encodes a corepressor protein that interacts with thyroid hormone receptors, providing insights into hair loss syndromes in humans and mice.

research Atrichia Caused by Mutations in the Vitamin D Receptor Gene Is a Phenocopy of Generalized Atrichia Caused by Mutations in the Hairless Gene

139 citations , September 2001 in “The journal of investigative dermatology/Journal of investigative dermatology”

This case report describes a patient with mutations in both alleles of the vitamin D receptor who exhibited hair loss clinically indistinguishable from generalized atrichia with papules, suggesting a potential genetic pathway shared with the hairless gene.

research Skin Abnormalities Generated by Temporally Controlled RXRα Mutations in Mouse Epidermis

303 citations , October 2000 in “Nature”

This study found that RXRα plays a critical role in hair cycling and keratinocyte functions in mice, likely through its interaction with VDR in epidermal cells.

research A Novel Missense Mutation (C622G) in the Zinc-Finger Domain of the Human Hairless Gene Associated with Congenital Atrichia with Papular Lesions

47 citations , April 2000 in “Experimental Dermatology”

This study identified a novel missense mutation in the hairless gene in a Polish family, which may contribute to congenital atrichia with papular lesions by affecting the gene's function.

research A Missense Mutation in the Zinc-Finger Domain of the Human Hairless Gene Underlies Congenital Atrichia in a Family of Irish Travellers

83 citations , October 1998 in “The American Journal of Human Genetics”

A specific gene mutation causes complete hair loss in an Irish Traveller family.