title: Expression of Bmi-1 in epidermis enhances cell survival by altering cell cycle regulatory protein expression and inhibiting apoptosis.
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.
authors.affiliation: Department of Physiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Lee
authors.forename: Gautam
authors.initials: G
authors.lastname: Adhikary
authors.forename: Sivaprakasam
authors.initials: S
authors.lastname: Balasubramanian
authors.forename: Ramamurthy
authors.initials: R
authors.lastname: Gopalakrishnan
authors.forename: Thomas
authors.initials: T
authors.lastname: McCormick
authors.forename: Goberdhan P
authors.initials: GP
authors.lastname: Dimri
authors.forename: Richard L
authors.initials: RL
authors.lastname: Eckert
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Rorke
mesh_terms: 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
chemical_list: 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