A mutation in protein phosphatase type 2A as a cause of melanoma progression.
The BL6 subline was derived from the F10 line, which was derived from the B16 mouse melanoma cell line. BL6 cells are more invasive than F10 cells and differ genetically from F10 cells by an alteration of the gene encoding the B56gamma regulatory subunit of protein phosphatase 2A (PP2A). This alteration results in the transcription of mRNA encoding a truncated variant of the B56gamma1 isoform (Delta-gamma-1). Delta-gamma-1 is capable of targeting PP2A to the specific subcellular sites but incapable of promoting the dephosphorylation of specific substrates that is normally mediated by the B56gamma subunit-containing PP2A holoenzyme. It thus appears that activities of this type of holoenzymes decrease in cells expressing Delta-gamma-1. Recently, we found two possible ways how Delta-gamma-1 contributes to the enhanced metastatic potential of BL6 cells. The two ways seemed far away from each other: Delta-gamma-1 influenced both the nuclear and cytoplasmic functions of the cell. In the cytoplasm, Delta-gamma-1 localized at the Golgi complex and accelerated Golgi-mediated vesicle transport. On the other hand, Delta-gamma-1 disturbed the cell-cycle regulation. In response to gamma-irradiation, protein levels of Delta-gamma-1 were markedly increased in BL6 cells. Subsequently the integrity of cell-cycle checkpoint became more aberrant in BL6 cells than that in F10 cells. These two actions of Delta-gamma-1 could results in the enhancement of the malignant phenotypes of melanoma cells, as discussed in this review.
Ito
A
A
Department of Pathology, Osaka University Medical School, Osaka, Japan. aito@patho.med.osaka-u.ac.jp
Koma
Y-I
YI
Watabe
K
K
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D006056:Golgi Apparatus / Q000502:physiology; D008546:Melanoma, Experimental / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D009154:Mutation / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D054648:Protein Phosphatase 2; D021381:Protein Transport / Q000235:genetics / Q000502:physiology
D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2