NEW NUCLEAR FUNCTIONS FOR CALMODULIN

The data reported here summarize a series of results which reveal new functions for nuclear calmodulin (CaM). The addition of CaM inhibitors to cultures of proliferating NRK cells blocked the activity of the cy clin-dependent protein kinases 4 (cdk4) and 2 (cdk2), which are enzyme s implicated in the progression of Gf and in the onset of DNA replicat ion, respectively. CaM modulates the activity of cdk4 by regulating th e nuclear location of both cdk4 and cyclin D, its associated regulator y subunit. By using CaM-affinity chromatography, we have recently iden tified two new nuclear CaM-binding proteins: (i) the protein La/SSB, w hich is an autoantigen implicated in several autoimmune diseases such as lupus erythematosus and Sjogren's syndrome (since La/SSB participat es in the process of transcription mediated by RNA polymerase ill, CaM could be involved in the regulation of this process); and (ii) the pr otein SAP145, a member of the spliceosome-associated proteins (SAPs) w hich is a subunit of the splicing factor SF3(b). This finding suggests the involvement of CaM in pre-mRNA splicing. Finally, a screening for new CaM-binding proteins in the fission yeast performed by using the phage display analysis, revealed that several nucleolar-ribosomal prot eins associate to CaM, suggesting that CaM modulates ribosomal assembl y and/or function.