The existence and function of inositide signaling in the nucleus is well documented and we know that the existence of the inositide cycle inside the nucleus has a biological role. An autonomous lipiddependent signaling system, independently regulated from its plasma membrane counterpart, acts in the nucleus and modulates cell cycle progression and differentiation.We and others focused on PLCb1, which is the most extensively investigated PLC isoform in the nuclear compartment. PLCb1 is a key player in the regulation of nuclear inositol lipid signaling, and, as discussed above, its function could also be involved in nuclear structure because it hydrolyses PtdIns(4,5)P2, a well accepted regulator of chromatin remodelling. The evidence, in a number of patients with myelodysplastic syndromes, that the mono-allelic deletion of PLCb1 is associated with an increased risk of developing acute myeloid leukemia paves the way for an entirely new field of investigation. Indeed the genetic defect evidenced, in addition to being a useful prognostic tool, also suggests that altered expression of this enzyme could have a role in the pathogenesis of this disease, by causing an imbalance between proliferation and apoptosis. The epigenetics of PLCb1 expression in MDS has been reviewed as well.
Cocco L, Follo MY, Faenza I, Fiume R, Ramazzotti G, Weber G, et al. (2011). Physiology and pathology of nuclear phospholipase C beta1. ADVANCES IN ENZYME REGULATION, 51, 2-12 [10.1016/j.advenzreg.2010.09.015].
Physiology and pathology of nuclear phospholipase C beta1
COCCO, LUCIO ILDEBRANDO;FOLLO, MATILDE YUNG;FAENZA, IRENE;FIUME, ROBERTA;RAMAZZOTTI, GIULIA;MARTELLI, ALBERTO MARIA;MANZOLI, FRANCESCO ANTONIO
2011
Abstract
The existence and function of inositide signaling in the nucleus is well documented and we know that the existence of the inositide cycle inside the nucleus has a biological role. An autonomous lipiddependent signaling system, independently regulated from its plasma membrane counterpart, acts in the nucleus and modulates cell cycle progression and differentiation.We and others focused on PLCb1, which is the most extensively investigated PLC isoform in the nuclear compartment. PLCb1 is a key player in the regulation of nuclear inositol lipid signaling, and, as discussed above, its function could also be involved in nuclear structure because it hydrolyses PtdIns(4,5)P2, a well accepted regulator of chromatin remodelling. The evidence, in a number of patients with myelodysplastic syndromes, that the mono-allelic deletion of PLCb1 is associated with an increased risk of developing acute myeloid leukemia paves the way for an entirely new field of investigation. Indeed the genetic defect evidenced, in addition to being a useful prognostic tool, also suggests that altered expression of this enzyme could have a role in the pathogenesis of this disease, by causing an imbalance between proliferation and apoptosis. The epigenetics of PLCb1 expression in MDS has been reviewed as well.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.