Journal Article

Identification and Functional Characterization of a TIA-1-Related Nucleolysin

Streuli, Michel, Tian, Qingsheng, Kawakami, Atsushi, Duan, Xiaochu, Anderson, Paul, Schlossman, Stuart F.

1992

Overview

We recently reported the molecular cloning of a cytotoxic granule-associated RNA-binding protein designated TIA-1. The ability of recombinant TIA-1 to induce DNA fragmentation in permeabilized cells suggested that this protein is the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets. Here we report the characterization of a cDNA encoding a TIA-1-related protein designated TIAR. The deduced amino acid sequence of TIAR reveals it to be a 42-kDa protein possessing three RNA-binding domains and a carboxyl-terminal auxiliary domain. Although the RNA-binding domains of TIA-1 and TIAR share >85% amino acid homology, their carboxyl-terminal auxiliary domains are only 51% homologous. The carboxyl terminus of TIAR contains a lysosome-targeting motif, indicating that TIAR is probably a cytotoxic granule-associated protein. Like TIA-1, purified recombinant TIAR induced DNA fragmentation in permeabilized target cells. Although immunoblotting analysis of post-nuclear supernatants revealed TIA-1 protein to be restricted to CTLs, PCR analysis revealed the expression of TIA-1 and TIAR mRNA transcripts in a wide variety of cell types. Our data suggest that the granules of CTLs contain at least two candidate nucleolysins involved in CTL killing.

• Publisher: National Academy of Sciences of the United States of America,National Acad Sciences,National Academy of Sciences
• Subject: Ageing, cell death / Amino Acid Sequence / Amino acids / Antibodies, Monoclonal - immunology / Base Sequence / Biological and medical sciences / Blotting, Southern / Cell Nucleus - drug effects / Cell physiology / Cloning, Molecular / Complementary DNA / Consensus Sequence / Cytotoxicity, Immunologic / Deoxyribonucleic acid / DNA / DNA - genetics / DNA Damage / DNA fragmentation / Fundamental and applied biological sciences. Psychology / Gene Expression / Generally accepted auditing standards / Genes / Humans / Immunity (Disease) / Lymphocytes / Medical research / Molecular and cellular biology / Molecular Sequence Data / Natural killer cells / Poly(A)-Binding Proteins - chemistry / Poly(A)-Binding Proteins - genetics / Poly(A)-Binding Proteins - metabolism / Polymerase chain reaction / Proteins / RNA, Messenger - genetics / RNA-Binding Proteins - chemistry / RNA-Binding Proteins - genetics / RNA-Binding Proteins - metabolism / Sequence Alignment / T lymphocytes / T-Cell Intracellular Antigen-1