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

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The mammalian hairless protein (HR) is a 130kDa nuclear transcription factor that is essential for proper skin and hair follicle function. Previous studies have focused on the role of HR in skin maintenance and hair cycling. However, the hairless gene (HR) is also expressed in brain and other tissues, where its role remains poorly understood. HR has been reported to contain functional domains that potentially serve in DNA binding, histone demethylation, nuclear translocation and protein-protein interactions. Indeed, HR has been shown to interact with and repress the action of the nuclear receptors for vitamin D and thyroid hormone as well as RAR-related orphan receptor alpha, possibly via recruitment of histone deacetylases. HR may also have important functions in non-skin tissues given that nearly 200 HR mutations have been identified in patients with various cancers, including prostate, breast, lung, melanoma, uterine, and glioma. This suggests that HR and/or mutants thereof have relevance to the growth and survival of cancer cells. For example, the reported intrinsic histone H3K9 demethylase activity of HR may activate dormant genes to contribute to carcinogenesis. Alternatively, the demonstrated ability of HR to interact with p53 and/or the p53 DNA response element to influence p53-regulated pathways may explain, at least in part, why many cancers express mutated HR proteins. In this review, we summarize the current knowledge of HR bioactions, how HR mutations may be contributing to alopecia as well as to cancer, and, finally, outline future directions in the study of this largely enigmatic nuclear protein.

Original languageEnglish (US)
JournalJournal of Cellular Biochemistry
DOIs
StateAccepted/In press - 2017

Fingerprint

Brain Neoplasms
Hair
Brain
Skin
Proteins
Nuclear Proteins
human HR protein
Histone Demethylases
Genes
Neoplasms
Mutation
Tissue
Histone Deacetylases
Hair Follicle
DNA
Alopecia
Response Elements
Mutant Proteins
Cytoplasmic and Nuclear Receptors
Thyroid Hormones

Keywords

  • ALOPECIA
  • GLIOBLASTOMA MULTIFORME
  • HISTONE H3K9 DEMETHYLASE
  • JmjC DOMAIN
  • SOMATIC MUTATION

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Human Hairless Protein Roles in Skin/Hair and Emerging Connections to Brain and Other Cancers. / Maatough, Anas; Whitfield, G Kerr; Brook, Lemlem; Hsieh, David; Palade, Patricia; Hsieh, Jui-Cheng.

In: Journal of Cellular Biochemistry, 2017.

Research output: Contribution to journalArticle

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