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

TLDR The hairless protein is important for skin, hair, and may influence cancer development.

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”

The Hr protein binds to DNA, interacts with p53, and affects cell cycle genes.

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”

HR protein causes abnormal hair cycles by increasing Tgf-β2 and reducing miR-31.

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”

Hairless protein affects hair follicle structure by regulating the Dlx3 gene.

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”

Certain mutations in the hairless protein disrupt its ability to regulate the hair cycle.

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”

Certain mutations in a hair growth-related gene cause a type of genetic 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”

The near-naked hairless mutation causes hair loss but is not due to a mutation in the hairless gene itself.

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

74 citations , September 2006 in “Cell Cycle”

The HR protein's role as a repressor is essential for controlling hair growth.

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”

Vitamin D receptor and hairless protein are essential for hair growth.

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

178 citations , October 2001 in “Genes & Development”

The mutated hairless gene causes hair loss by acting as a new type of corepressor affecting thyroid hormone receptors.

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”

Mutations in the Vitamin D receptor gene can cause hair loss similar to mutations in the Hairless gene.

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

303 citations , October 2000 in “Nature”

RXRα is crucial for hair growth and skin cell function.

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”

A new gene mutation causes a rare type of hair loss.

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.