title: Pituitary tumor-transforming gene 1 enhances proliferation and suppresses early differentiation of keratinocytes.
abstract: The epidermis is a self-renewing tissue, the homeostasis of which is dependent upon the tight balance between proliferation and differentiation based on appropriate regulation of the cell cycle. The cell cycle regulation is dependent on the interactions among a number of cell cycle regulatory molecules, including the pituitary tumor-transforming gene 1 (PTTG1), also known as securin, a regulator of sister chromatid separation and transition from metaphase to anaphase. This study was conducted to clarify the less-known functions of PTTG1 in the epidermis by the use of keratinocytes cultured under two-dimensional (2D) or three-dimensional (3D) conditions. Forced overexpression of PTTG1 caused upregulation of cyclin B1, cyclin-dependent kinase 1 (CDK1), and c-Myc, resulting in enhanced proliferation and suppression of early differentiation without apparent alterations in terminal differentiation, and the exogenous PTTG1 was downregulated in association with cell cycle exit. In contrast, depletion of PTTG1 caused their downregulation and constrained proliferation with retention of differentiation capacity. These findings suggested that PTTG1 could alter the proliferation status by modulating the expression levels of the other cell cycle regulatory proteins, and excess PTTG1 primarily affects early differentiation of keratinocytes under the stability regulation associated with cell cycle exit.
authors.affiliation: Department of Dermatology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ishitsuka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawachi
authors.forename: Shijima
authors.initials: S
authors.lastname: Taguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maruyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Furuta
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Fujio
authors.initials: F
authors.lastname: Otsuka
mesh_terms: D016203:CDC2 Protein Kinase / Q000502:physiology; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D056744:Cyclin B1 / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D064249:Securin
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; C489427:MYC protein, human; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D016203:CDC2 Protein Kinase