Functions of the histone chaperone nucleolin in diseases.

Alteration of nuclear morphology is often used by pathologist as diagnostic marker for malignancies like cancer. In particular, the staining of cells by the silver staining methods (AgNOR) has been proved to be an important tool for predicting the clinical outcome of some cancer diseases. Two major argyrophilic proteins responsible for the strong staining of cells in interphase are the nucleophosmin (B23) and the nucleolin (C23) nucleolar proteins. Interestingly these two proteins have been described as chromatin associated proteins with histone chaperone activities and also as proteins able to regulate chromatin transcription. Nucleolin seems to be over-expressed in highly proliferative cells and is involved in many aspect of gene expression: chromatin remodeling, DNA recombination and replication, RNA transcription by RNA polymerase I and II, rRNA processing, mRNA stabilisation, cytokinesis and apoptosis. Interestingly, nucleolin is also found on the cell surface in a wide range of cancer cells, a property which is being used as a marker for the diagnosis of cancer and for the development of anti-cancer drugs to inhibit proliferation of cancer cells. In addition to its implication in cancer, nucleolin has been described not only as a marker or as a protein being involved in many diseases like viral infections, autoimmune diseases, Alzheimer's disease pathology but also in drug resistance. In this review we will focus on the chromatin associated functions of nucleolin and discuss the functions of nucleolin or its use as diagnostic marker and as a target for therapy