title: Galectin-3 regulates p21 stability in human prostate cancer cells.
abstract: Galectin-3 (Gal-3) is a multifunctional protein involved in cancer through regulation of cell adhesion, cell growth, apoptosis and metastasis, while p21 (Cip1/WAF1) is a negative regulator of the cell cycle, involved in apoptosis, transcription, DNA repair and metastasis. The results presented here demonstrate for the first time that the level of Gal-3 protein is associated with the level of p21 protein expression in human prostate cancer cells and the effects of Gal-3 on cell growth and apoptosis were reversed by modulating p21 expression level. Furthermore, Gal-3 regulates p21 expression at the post-translational level by stabilizing p21 protein via the carbohydrate-recognition domain. This is the first report suggesting a molecular function not yet described for Gal-3 as the regulator of p21 protein stability. This study provides a unique insight into the relationship of these two molecules during prostate cancer progression, and may provide a novel therapeutic target.
authors.affiliation: Department of Oncology, Tumor Progression and Metastasis, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: V
authors.initials: V
authors.lastname: Balan
authors.forename: D
authors.initials: D
authors.lastname: Kho
authors.forename: V
authors.initials: V
authors.lastname: Hogan
authors.forename: P
authors.initials: P
authors.lastname: Nangia-Makker
authors.forename: A
authors.initials: A
authors.lastname: Raz
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D001798:Blood Proteins; D003198:Computer Simulation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D037161:Galectins; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D014407:Tumor Cells, Cultured
chemical_list: D001798:Blood Proteins; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human