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Published on: December 14, 2015
Changes in HOXB6 homeodomain protein structure and localization during human epidermal development and
L G Kömüves1, W F Shen, A Kwong
1Department of Dermatology, University of California VA Medical Center, San Francisco, California.
Summary
HOX homeodomain proteins regulate development. In adult skin, HOXB6 shifts from cytoplasmic to nuclear, but doesn't bind DNA with PBX partners, suggesting alternative functions for truncated HOXB6 isoforms.
Area of Science:
- Developmental Biology
- Molecular Biology
- Dermatology
Background:
- HOX homeodomain proteins are critical developmental regulators.
- They are believed to function as transcription factors through cooperative DNA binding with PBX proteins.
- Limited data exists on HOX and PBX protein localization during skin development.
Purpose of the Study:
- To investigate the localization and potential function of HOXB6 and PBX proteins during human skin development.
- To determine if HOXB6 and PBX proteins co-localize in the nucleus in skin.
- To explore the role of different HOXB6 isoforms in epidermal differentiation.
Main Methods:
- Immunohistochemistry to detect HOXB6 and PBX protein expression and localization in fetal and adult human skin.
- Analysis of HOXB6 protein localization in hyperproliferative skin conditions and carcinomas.
- Use of GFP-fusion proteins to assess the subcellular localization of full-length and truncated HOXB6 proteins.
Main Results:
- HOXB6 is expressed in the suprabasal epidermis, with a shift from cytoplasmic localization in fetal skin to nuclear localization in adult skin.
- HOXB6 is partially nuclear in hyperproliferative conditions but cytoplasmic in basal and squamous cell carcinomas.
- No nuclear co-localization of HOXB6 with any of the three PBX proteins was observed in fetal or adult epidermis.
- A truncated, non-homeodomain HOXB6 isoform is present in undifferentiated keratinocytes and is cytoplasmic, while full-length HOXB6 is induced by differentiation and localizes to the nucleus.
Conclusions:
- The subcellular localization of HOXB6 changes during epidermal development and differentiation.
- The truncated HOXB6 isoform may function independently of DNA binding in undifferentiated keratinocytes.
- Nuclear HOXB6 in adult skin does not appear to utilize PBX proteins as DNA-binding partners in the skin.
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