Interactions of the Vitamin D Receptor with the Corepressor Hairless

July 2007 in “ Journal of Biological Chemistry ”

Jining Wang, Peter J. Malloy, David Feldman

Vitamin D Receptor Hairless gene atrichia with papular lesions corepressor activity histone deacetylase 1 HR mutants VDR protein non-synonymous polymorphisms VDR HR gene APL HDAC1

TLDR Most Hairless gene mutations reduce its ability to work with the Vitamin D Receptor, which might explain a certain type of hair loss.

The document from August 1, 2007, investigated the interaction between the Vitamin D Receptor (VDR) and mutants of the Hairless (HR) gene, which is associated with atrichia with papular lesions (APL), a form of hair loss. The study found that most pathogenic HR mutants lost their corepressor activity on VDR, which could be due to impaired interactions with histone deacetylase 1 (HDAC1). However, one mutant, E583V, retained normal activity, suggesting it may not be pathogenic. HR variants from non-synonymous polymorphisms showed normal or partially reduced corepressor activity. All pathogenic mutants and variants increased the level of VDR protein when coexpressed, indicating that this HR function was not affected by the mutations. The study provided insight into the molecular basis of APL by showing how HR mutations impact VDR corepressor activity.

View this study on jbc.org →

Discuss this study in the Community →

Research cited in this study

24 / 24 results

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 Atrichia With Papular Lesions Resulting From a Novel Insertion Mutation in the Human Hairless Gene

19 citations , May 2006 in “Clinical and Experimental Dermatology”

Researchers found a new mutation causing total hair loss from birth.

research A Novel Missense Mutation in the Mouse Hairless Gene Causes Irreversible Hair Loss: Genetic and Molecular Analyses of Hrm1Enu

18 citations , February 2006 in “Genomics”

A new genetic mutation in mice causes permanent hair loss and skin wrinkling.

research Development and Progression of Alopecia in the Vitamin D Receptor Null Mouse

81 citations , January 2006 in “Journal of cellular physiology”

Mice without the vitamin D receptor gene lose hair due to disrupted hair follicle cycles.

research Hairless Suppresses Vitamin D Receptor Transactivation in Human Keratinocytes

78 citations , November 2005 in “Endocrinology”

Hairless protein can block vitamin D activation in skin cells.

research Atrichia With Papular Lesions in Two Pakistani Consanguineous Families Resulting From Mutations in the Human Hairless Gene

20 citations , October 2005 in “Archives of Dermatological Research”

research Hairless Triggers Reactivation of Hair Growth by Promoting Wnt Signaling

137 citations , September 2005 in “Proceedings of the National Academy of Sciences of the United States of America”

The HR protein helps hair grow by blocking a hair growth inhibitor, aiding in hair follicle regeneration.

research Ligand-Independent Actions of the Vitamin D Receptor Maintain Hair Follicle Homeostasis

144 citations , December 2004 in “Molecular Endocrinology”

The vitamin D receptor is essential for normal hair growth, even without its usual binding.

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 Atrichia With Papular Lesions Resulting From a Novel Homozygous Missense Mutation in the Hairless Gene

20 citations , August 2003 in “Clinical and Experimental Dermatology”

A new genetic mutation in the hairless gene causes a rare hair loss disorder.

research Compound Heterozygous Mutations in the Hairless Gene in Atrichia with Papular Lesions

23 citations , July 2003 in “Journal of Investigative Dermatology”

Genetic testing for hairless gene mutations is crucial to correctly diagnose and treat atrichia with papular lesions.

research A Novel Missense Mutation Affecting the Human Hairless Thyroid Receptor Interacting Domain 2 Causes Congenital Atrichia

26 citations , October 2002 in “Journal of Investigative Dermatology”

A specific gene mutation causes congenital hair loss.

research Clinical and Molecular Diagnostic Criteria of Congenital Atrichia with Papular Lesions

69 citations , May 2002 in “Journal of Investigative Dermatology”

Congenital atrichia with papular lesions is often misdiagnosed, and new diagnostic criteria can improve accuracy.

research The Hairless Gene in Androgenetic Alopecia: Results of a Systematic Mutation Screening and a Family-Based Association Approach

15 citations , April 2002 in “British Journal of Dermatology”

Hairless gene not strongly linked to baldness.

Targeted Expression of Human Vitamin D Receptor in the Skin Promotes the Initiation of the Postnatal Hair Follicle Cycle and Rescues Alopecia in Vitamin D Receptor Null Mice

research Targeted Expression of Human Vitamin D Receptor in the Skin Promotes the Initiation of the Postnatal Hair Follicle Cycle and Rescues Alopecia in Vitamin D Receptor Null Mice

57 citations , April 2002 in “The journal of investigative dermatology/Journal of investigative dermatology”

Vitamin D receptor is crucial for starting hair growth after birth.

research Targeting Expression of the Human Vitamin D Receptor to the Keratinocytes of Vitamin D Receptor Null Mice Prevents Alopecia

115 citations , December 2001 in “Endocrinology”

Expressing the human vitamin D receptor in skin cells prevents hair loss in certain mice.

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 Variant 1859G→A (Arg620Gln) of the Hairless Gene: Absence of Association with Papular Atrichia or Androgenetic Alopecia

14 citations , July 2001 in “American Journal of Human Genetics”

Haplogroup X found in Altaian population supports Amerindian origin.

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 Novel Hairless Mutations in Two Kindreds with Autosomal Recessive Papular Atrichia

66 citations , December 1999 in “Journal of Investigative Dermatology”

New mutations in the hairless gene may cause hair loss and affect bone development.

research A Homozygous Nonsense Mutation in the Zinc-Finger Domain of the Human Hairless Gene Underlies Congenital Atrichia

37 citations , August 1999 in “Journal of Investigative Dermatology”

A specific gene mutation causes complete hair loss without other health issues.

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.

research Alopecia Universalis Associated With a Mutation in the Human Hairless Gene

412 citations , January 1998 in “Science”

A mutation in the human hairless gene causes alopecia universalis.

Related Research

10 / 10 results

research Novel Mechanisms for the Vitamin D Receptor in the Skin and in Skin Cancer

71 citations , October 2014 in “The Journal of Steroid Biochemistry and Molecular Biology”

Vitamin D receptor helps prevent skin cancer and supports skin health.

research Vitamin D Receptor-Mediated Control of Soggy, Wise, and Hairless Gene Expression in Keratinocytes

13 citations , November 2013 in “Journal of Endocrinology/Journal of endocrinology”

Vitamin D receptor helps control hair growth genes in skin cells.

research Vitamin D and the Skin: Physiology and Pathophysiology

158 citations , August 2011 in “Reviews in endocrine and metabolic disorders”

Vitamin D and its receptor regulate skin functions like cell growth, immunity, hair cycle, and tumor prevention.

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.

research Vitamin D and the Skin

76 citations , January 2010 in “Journal of bone and mineral metabolism”

research Quantification of the Vitamin D Receptor-Coregulator Interaction

62 citations , January 2009 in “Biochemistry”

Vitamin D receptor binds similarly to natural and synthetic ligands, affecting gene regulation.

research Hairless Protein of Jumonji Family and Hair Loss

January 2009

Mutations in the hairless protein gene cause hair loss.

Vitamin D Receptor: Molecular Signaling and Actions of Nutritional Ligands in Disease Prevention