Nuclear but not cytoplasmic phospholipase C β1 inhibits differentiation of erythroleukemia cells

Alessandro Matteucci, Irene Faenza, R. Stewart Gilmour, Lucia Manzoli, Anna Maria Billi, Daniela Peruzzi, Alberto Bavelloni, Sue Goo Rhee, Lucio Cocco

Research output: Contribution to journalArticlepeer-review


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 β family is characterized by a long COOH-terminal tail that contains a cluster of lysine residues responsible for nuclear localization. Indeed, PLCβ1 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, PLCOβ1 is down-regulated during the erythroid differentiation of Friend erythroleukemia cells. A key question is how PLCβ1 signaling at the nucleus fits into the erythroid differentiation program of Friend erythroleukemia cells, and whether PLCβ1 signaling activity is directly responsible for the maintenance of the undifferentiated state of erythroleukemia cells. Here we present evidence that nuclear PLCβ1 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 PLCβ1 is overexpressed in these cells, differentiation in response to DMSO is inhibited in that the expression of β-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 β-globin is the same as in wild-type cells.

Original languageEnglish
Pages (from-to)5057-5060
Number of pages4
JournalCancer Research
Issue number22
Publication statusPublished - Nov 15 1998

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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