Pocket protein function in melanocyte homeostasis and neoplasia.
Melanoma is the most lethal of human skin cancers and its incidence is increasing worldwide [L.K. Dennis (1999). Arch. Dermatol. 135, 275; C. Garbe et al. (2000). Cancer 89, 1269]. Melanomas often metastasize early during the course of the disease and are then highly intractable to current therapeutic regimens [M.F. Demierre and G. Merlino (2004). Curr. Oncol. Rep. 6, 406]. Consequently, understanding the factors that maintain melanocyte homeostasis and prevent their neoplastic transformation into melanoma is of utmost interest from the perspective of therapeutic interdiction. This review will focus on the role of the pocket proteins (PPs), Rb1 (retinoblastoma protein), retinoblastoma-like 1 (Rbl1 also known as p107) and retinoblastoma-like 2 (Rbl2 also known as p130), in melanocyte homeostasis, with particular emphasis on their functions in the cell cycle and the DNA damage repair response. The potential mechanisms of PP deregulation in melanoma and the possibility of PP-independent pathways to melanoma development will also be considered. Finally, the role of the PP family in ultraviolet radiation (UVR)-induced melanoma and the precise contribution that each PP family member makes to melanocyte homeostasis will be discussed in the context of a number of genetically engineered mouse models.
Tonks
Ian D
ID
Queensland Institute of Medical Research, Herston, Brisbane, Queensland, Australia. ian.tonks@qimr.edu.au
Hayward
Nicholas K
NK
Kay
Graham F
GF
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D004249:DNA Damage / Q000528:radiation effects; D006706:Homeostasis; D006801:Humans; D008544:Melanocytes / Q000502:physiology*; D008545:Melanoma / Q000503:physiopathology*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000502:physiology; D023421:Models, Animal; D008954:Models, Biological; D009381:Neoplasms, Radiation-Induced; D016160:Retinoblastoma Protein / Q000502:physiology*; D050720:Retinoblastoma-Like Protein p107 / Q000502:physiology*; D050717:Retinoblastoma-Like Protein p130 / Q000502:physiology*; D015398:Signal Transduction; D014466:Ultraviolet Rays / Q000009:adverse effects
D051739:Microphthalmia-Associated Transcription Factor; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130