Expression of Bmi-1 in epidermis enhances cell survival by altering cell cycle regulatory protein expression and inhibiting apoptosis.
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.
Lee
Kathy
K
Department of Physiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Adhikary
Gautam
G
Balasubramanian
Sivaprakasam
S
Gopalakrishnan
Ramamurthy
R
McCormick
Thomas
T
Dimri
Goberdhan P
GP
Eckert
Richard L
RL
Rorke
Ellen A
EA
D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics*; D002470:Cell Survival; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000032:analysis; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D051379:Mice; D016513:Mice, SCID; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D011565:Psoriasis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012878:Skin Neoplasms / Q000378:metabolism
C069077:BMI1 protein, human; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C062521:RCC1 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; D019938:Cyclin D1; D063150:Polycomb Repressive Complex 1