Document Detail

Inositol lipid cycle and autonomous nuclear signalling.
MedLine Citation:
PMID:  8869743     Owner:  NLM     Status:  MEDLINE    
The involvement of phospholipids and in particular polyphosphoinositides in cellular signalling has been documented in detail in the last 20 years. In addition to the plasma membrane localization also the nucleus is shown to be a site for both synthesis and hydrolysis of the phosphorylated forms of phosphatidylinositol. Previous observation have established that the nucleus possesses a specific PLC for inositol lipids, i.e., the PLC beta 1 isoform, which undergoes rapid and transient activation after IGF-I stimulation of quiescent Swiss 3T3 cells and is down-regulated after treatment of Friend erythroleukemia cells with DMSO. Here we have reviewed: (i) the potential of nuclear PLC beta 1 to be a target for anti-cancer drug, (ii) the capability of this PLC isoform, when activated by IGF-I, to be a key signalling molecule in the onset of DNA synthesis, via DAG generation and PKC alpha translocation to the nucleus, (iii) the chromosome mapping of PLC beta 1 gene. The differentiation program of Friend cells can be activated by other agents besides DMSO including tiazofurin, an anti-tumor drug, also capable of affecting the nuclear inositol lipid cycle. Tiazofurin induces a lowering of the activity of PLC beta 1 due to down regulation of this isoform as revealed by both Western blotting and Northern blotting analyses. Using Swiss 3T3 cells stably transformed with an antisense PLC beta 1 construct, the knock-out of the PLC beta 1 gene induces both a loss of PLC beta 1 expression, as determined by Western blots, and a loss of the mitogenic responsiveness to IGF-I. These events show a direct relationship between nuclear PLC beta 1 evoked signals and IGF-I induced cell proliferation. Finally, the assignment of the PLC beta 1 gene to the band q35-36 of rat chromosome 3 paves the way for further genetic studies given the fact that the region where PLC beta 1 gene maps is a hot spot for genetic alterations in a number of experimentally induced rat tumors. Taken as a whole, these results assign a key role to the regulation of nuclear PLC activity and expression both in growth-factor activated mitogenesis and in in vitro erythroid differentiation.
L Cocco; S Capitani; N M Maraldi; G Mazzotti; O Barnabei; R S Gilmour; F A Manzoli
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Advances in enzyme regulation     Volume:  36     ISSN:  0065-2571     ISO Abbreviation:  Adv. Enzyme Regul.     Publication Date:  1996  
Date Detail:
Created Date:  1996-12-30     Completed Date:  1996-12-30     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0044263     Medline TA:  Adv Enzyme Regul     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  101-14     Citation Subset:  IM    
Institute of Human Anatomy, University of Bologna, Italy.
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MeSH Terms
Antineoplastic Agents / metabolism,  pharmacology
Blotting, Northern
Blotting, Western
Cell Nucleus / metabolism*
Isoenzymes / antagonists & inhibitors,  metabolism*
Lipid Metabolism
Phosphatidylinositols / metabolism*
Phospholipase C beta
Protein Kinase C / metabolism
Ribavirin / analogs & derivatives,  pharmacology
Signal Transduction / physiology
Type C Phospholipases / antagonists & inhibitors,  metabolism*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Isoenzymes; 0/Phosphatidylinositols; 36791-04-5/Ribavirin; 60084-10-8/tiazofurin; EC Kinase C; EC 3.1.4.-/Type C Phospholipases; EC C beta; EC protein, rat

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