Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family.
Galectin-3, a beta-galactoside-binding protein, has been shown to be involved in tumor progression and metastasis. Here, we demonstrate that expression of galectin-3 in human breast carcinoma BT549 cells inhibits cis-diamminedichloroplatinum (cisplatin)-induced poly(ADP-ribose) polymerase degradation and apoptosis, without altering Bcl-2, Bcl-X(L), or Bax expressions. Galectin-3 contains the NWGR amino acid sequence highly conserved in the BH1 domain of the bcl-2 gene family, and a substitution of glycine to alanine in this motif abrogated its antiapoptotic activity. Our findings demonstrate that galectin-3 inhibits apoptosis through a cysteine protease pathway and highlight the functional significance of the NWGR motif in apoptosis resistance of a non-Bcl-2 protein.
Akahani
S
S
Tumor Progression and Metastasis Program, Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
Nangia-Makker
P
P
Inohara
H
H
Kim
H R
HR
Raz
A
A
D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D017124:Conserved Sequence; D053938:DNA Fragmentation; D005260:Female; D037502:Galectin 3; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008969:Molecular Sequence Data; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000943:Antigens, Differentiation; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D037502:Galectin 3; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D011065:Poly(ADP-ribose) Polymerases; D002945:Cisplatin