Nuclear but not cytoplasmic phospholipase C beta 1 inhibits differentiation of erythroleukemia cells.
A body of evidence has shown the existence of a nuclear phosphoinositide cycle in different cell types. The cycle is endowed with kinases as well as phosphatases and phospholipase C (PLC). Among the PLC isozymes, the beta family is characterized by a long COOH-terminal tail that contains a cluster of lysine residues responsible for nuclear localization. Indeed, PLC beta 1 is the major isoform that has been detected in the nucleus of several cells. This isoform is activated by insulin-like growth factor I, and when this isoform is lacking, as a result of gene ablation, the onset of DNA synthesis induced by this hormone is abolished. On the contrary, PLC beta 1 is down-regulated during the erythroid differentiation of Friend erythroleukemia cells. A key question is how PLC beta 1 signaling at the nucleus fits into the erythroid differentiation program of Friend erythroleukemia cells, and whether PLC beta 1 signaling activity is directly responsible for the maintenance of the undifferentiated state of erythroleukemia cells. Here we present evidence that nuclear PLC beta 1 but not the isoform located at the plasma membrane is directly involved in maintaining the undifferentiated state of Friend erythroleukemia cells. Indeed, when wild-type PLC beta 1 is overexpressed in these cells, differentiation in response to DMSO is inhibited in that the expression of beta-globin is almost completely abolished, whereas when a mutant lacking the ability to localize to the nucleus is expressed, the cells differentiate, and the expression of beta-globin is the same as in wild-type cells.
Matteucci
A
A
Consiglio Nazionale delle Ricerche and Cell Biology Laboratory, Istituto Rizzoli, Bologna, Italy.
Faenza
I
I
Gilmour
R S
RS
Manzoli
L
L
Billi
A M
AM
Peruzzi
D
D
Bavelloni
A
A
Rhee
S G
SG
Cocco
L
L
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000201:enzymology*; D003593:Cytoplasm / Q000201:enzymology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005622:Friend murine leukemia virus; D005914:Globins / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D054799:Phospholipase C beta; D012997:Solvents / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000235:genetics / Q000502:physiology*
D007527:Isoenzymes; D012997:Solvents; D005914:Globins; D010738:Type C Phospholipases; D054799:Phospholipase C beta; C518034:Plcb1 protein, mouse; D004121:Dimethyl Sulfoxide