Molecular dissection of nucleolin's role in growth and cell proliferation:new insights

M. Srivastava et Hb. Pollard, Molecular dissection of nucleolin's role in growth and cell proliferation:new insights, FASEB J, 13(14), 1999, pp. 1911-1922
Citations number
Categorie Soggetti
Experimental Biology
Journal title
ISSN journal
0892-6638 → ACNP
Year of publication
1911 - 1922
SICI code
Cells require optimum protein synthetic activity in order to support cell p roliferation, maintain homeostatic and metabolic integrity, and repair dama ge. Since growth depends on protein synthesis through ribosome biogenesis, the control of biosynthesis of ribosomes is necessarily a key element for c ontrol of growth. Nucleolin is a major nucleolar protein of exponentially g rowing eukaryotic cells, which is directly involved in the regulation of ri bosome biogenesis and maturation. The highly conserved nucleolin contains t hree major domains through which it controls the organization of nucleolar chromatin, packaging of pre-RNA, rDNA transcription, and ribosome assembly. Numerous reports have implicated the involvement of nucleolin either direc tly or indirectly in the regulation of cell proliferation and growth, cytok inesis, replication, embryogenesis, and nucleogenesis, Nucleolin, an RNA bi nding protein, is also an autoantigen, a transcriptional repressor, and a s witch region targeting factor. In addition, nucleolin exhibits autodegradat ion, DNA and RNA helicase activities, and DNA-dependent ATPase activity. An interesting aspect of nucleolin action is that it is a target for regulati on by proteolysis, methylation, ADP-ribosylation, and phosphorylation by CK II, cdc2, PKC-xi, cyclic AMP-dependent protein kinase, and ecto-protein kin ase. For these and other reasons, nucleolin is fundamental to the survival and proliferation of cells. Considerable progress has been made in recent y ears with the identification of new nucleolin binding proteins that may med iate these many nucleolin-dependent functions. Nucleolin also functions as a cell surface receptor, where it acts as a shuttling protein between cytop lasm and nucleus, and thus can even provide a mechanism for extracellular r egulation of nuclear events. Exploration of the regulation of this multifac eted protein in a remarkable number of diverse functions is challenginp.-Sr ivastava, M., Pollard, Il. B. Molecular dissection of nucleolin's role in g rowth and cell proliferation: new insights.