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PMID: 17625597 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Expression of Bmi-1 in epidermis enhances cell survival by altering cell cycle regulatory protein expression and inhibiting apoptosis.

The Journal of investigative dermatology ·Vol. 128 ·No. 1 ·2008-01-00 ·Pages 9-17

Lee K, Adhikary G, Balasubramanian S, Gopalakrishnan R, McCormick T, Dimri GP, Eckert RL, Rorke EA

Abstract

The polycomb group (PcG) genes are epigenetic suppressors of gene expression that play an important role in development. In this study, we examine the role of Bmi-1 (B-cell-specific Moloney murine leukemia virus integration site 1) as a regulator of human epidermal keratinocyte survival. We identify Bmi-1 mRNA and protein expression in epidermis and in cultured human keratinocytes. Bmi-1 is located in the nucleus in cultured keratinocytes, and in epidermis it is expressed in the basal and suprabasal layers. Adenovirus-delivered Bmi-1 promotes keratinocyte survival and protects keratinocytes from stress agent-mediated cell death. This is associated with increased levels of cyclin D1 and selected cyclin-dependent kinases, and reduced caspase activity and poly(ADP-ribose) polymerase (PARP) cleavage. Bmi-1 may be involved in the maintenance of disease state, as Bmi-1 levels are elevated in transformed keratinocytes, skin tumors, and psoriasis. The presence of Bmi-1 in suprabasal non-proliferative cells of the epidermis and within a high percentage of cells within skin tumors suggests a non-stem cell pro-survival role for Bmi-1 in this tissue. Based on the suprabasal distribution of Bmi-1 in epidermis, we propose that Bmi-1 may promote maintenance of suprabasal keratinocyte survival to prevent premature death during differentiation. Such a function would help assure proper formation of the stratified epidermis.

MeSH Terms
Animals Apoptosis Cell Cycle Proteins/genetics Cell Survival Cells, Cultured Cyclin D1/analysis Epidermal Cells Epidermis/metabolism Guanine Nucleotide Exchange Factors/genetics Humans Keratinocytes/cytology,physiology Mice Mice, SCID Nuclear Proteins/genetics,physiology Polycomb Repressive Complex 1 Proto-Oncogene Proteins/genetics,physiology Psoriasis/metabolism RNA, Messenger/analysis Repressor Proteins/genetics,physiology Skin Neoplasms/metabolism
Chemicals
BMI1 protein, human Cell Cycle Proteins Guanine Nucleotide Exchange Factors Nuclear Proteins Proto-Oncogene Proteins RCC1 protein, human RNA, Messenger Repressor Proteins Cyclin D1 Polycomb Repressive Complex 1
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Lee Kathy
Department of Physiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Adhikary Gautam
Balasubramanian Sivaprakasam
Gopalakrishnan Ramamurthy
McCormick Thomas
Dimri Goberdhan P
Eckert Richard L
Rorke Ellen A
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Article Info
Journal
The Journal of investigative dermatology
Abbr.
J Invest Dermatol
ISSN
1523-1747
DOI
10.1038/sj.jid.5700949
Published
2008-01-00
Epub
2007-00-12
Pages
9-17
Language
English
Region
United States
NLM ID
0426720
PMCID
PMC3043461
Subset
IM
Grants
NCI NIH HHS · R01 CA131074-01A1 · United States
NIAMS NIH HHS · P30 AR039750 · United States
NIAMS NIH HHS · AR39750 · United States
NCI NIH HHS · P30 CA134274 · United States
NCI NIH HHS · R01 CA131074 · United States
NCI NIH HHS · R01 CA094150-05 · United States
NIAMS NIH HHS · R01 AR053851 · United States
NIAMS NIH HHS · R01 AR053851-01A2 · United States
NCI NIH HHS · R01 CA094150 · United States
External Links
PubMed source DOI: 10.1038/sj.jid.5700949 PMC Full Text View journal details
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