MULTIFUNCTIONAL CHARACTERIZATION OF HYALURONAN BINDING PROTEIN 1 OF HUMAN AS APOPTOTIC INDUCER AND ACTIVATOR OF MATRIX METALLOPROTEASES

Hyaluronan, an important constitutent of the extracellular matrix (ECM) is known to have multifaceted regulations through its different ligands like hyaluronic acid binding protein1 (HABP1). It has been purified, cloned and shown to be present in human chromosome 17p13.3. Sequence analysis confirmed its multifunctionlity as it is identical with p32, the protein associated with alternate splicing factor SF2 and the receptor of gC1Q. Interestingly its differential cellular compartmentalization in several cell lines and nuclear translocation with viral transformation raises its different activities residing in specific compartments. In order to search for its function, we have made the following approaches. We have transformed normal fibroblast with HABP1 gene and found it undergoes into apoptosis due to generation of reactive oxygen species by the mitochondrial accumulation of HABP1. In parallel, we investigated the probable pathway of cell cycle modulation in which expression of HABP1 has been down regulated by siRNA. In continuation as being an ECM component HA is known to promote anchorage independent growth and invasiveness, the mark of malignant phenotype. Thus we studied the effect of HABP1 supplementation in the medium and found enhanced expression and secretion of matrix metalloproteases which can be correlated with NF‐êB activation. Finally we would like to discuss earlier clinical reports on the level of HABP1 in carcinoma and papiloma with our present data on defined functions of HABP1 gene.