Biomedical subjects

Q A Liu

Publications and source records attributed to Q A Liu.

5 recordsLinked to original sources

PubMed1999

Human CED-6 encodes a functional homologue of the Caenorhabditis elegans engulfment protein CED-6.

The rapid engulfment of apoptotic cells is a specialized innate immune response used by organisms to remove apoptotic cells. In mammals, several receptors that recognize apoptotic cells have been identified; molecules that transduce signals from these receptors to downstream cytoskeleton molecules have not been found, however [1] [2] [3]. Our previous analysis of the engulfment gene ced-6 in Caenorhabditis elegans has suggested that CED-6 is an adaptor protein that participates in a signal transduction pathway that mediates the specific recognition and engulfment of apoptotic cells [1]. Here, we describe our isolation and characterization of a human cDNA encoding a protein, hCED-6, with strong sequence similarity to C. elegans CED-6. As is the case with the worm protein, hCED-6 contains a phosphotyrosine-binding (PTB) domain and potential Src-homology domain 3 (SH3) binding sites. Both CED-6 and hCED-6 contain a predicted coiled-coil domain in the middle region. The hCED-6 protein lacks the extended carboxyl terminus found in worm CED-6; this carboxy-terminal extension appears not to be essential for CED-6 function in C. elegans, however. Overexpression of hCED-6 rescues the engulfment defect of ced-6 mutants in C. elegans significantly, suggesting that hCED-6 is a functional homologue of C. elegans CED-6. Human ced-6 is expressed widely in most human tissues. Thus, CED-6, and the CED-6 signal transduction pathway, might be conserved from C. elegans to humans and are present in most, if not all, human tissues.

Amino Acid Sequence↗

PubMed1999

The molecular mechanism of programmed cell death in C. elegans.

Programmed cell death or apoptosis plays a fundamental role during animal development, metamorphosis, and tissue homeostasis. It is a genetically controlled physiological process that comprises two distinct and sequential processes: the death of cells, and their subsequent removal by engulfing cells. In the nematode C. elegans, genetic studies led to the discovery of 15 genes that function in programmed cell death (FIG. 1). These 15 genes have been divided into four groups based on the order of their activity during the process of programmed cell death: (1) those involved in the decision making (ces-1 and ces-2); (2) in the process of execution (ced-3, ced-4, ced-9 and egl-1); (3) in the engulfment of dying cells by engulfing cells (ced-1, ced-2, ced-5, ced-6, ced-7, ced-10, ced-12); and (4) those in the degradation of cell corpses within engulfing cells (nuc-1). In the last five years, several genes in the genetic pathway of programmed cell death have been shown to be conserved across a wide range of species; all genes involved in the step of execution in C. elegans have their corresponding mammalian homologs (FIG. 2). Furthermore, emerging evidence from molecular studies of engulfment genes in several species suggests that the signaling process from apoptotic cells to engulfing cells and the subsequent engulfment process might be also conserved across species (TABLE 1).

Animals↗

PubMed1998

Candidate adaptor protein CED-6 promotes the engulfment of apoptotic cells in C. elegans.

The rapid engulfment (phagocytosis) of cells undergoing programmed cell death (apoptosis) is a fundamental biological process that is not well understood. Here we report the cloning and functional characterization of ced-6, a gene specifically required for the engulfment of apoptotic cells in the nematode C. elegans. The CED-6 protein contains a phosphotyrosine binding domain at its N terminus and a proline/serine-rich region in its C-terminal half. Genetic mosaic analysis demonstrates that ced-6 acts within engulfing cells. We also show that ced-6 can promote the engulfment of cells at both early and late stages of apoptosis. Our data suggest that CED-6 is an adaptor molecule acting in a signal transduction pathway that specifically mediates the recognition and engulfment of apoptotic cells.

Amino Acid Sequence↗

PubMed1991

The inhibition of restriction endonuclease PvuII cleavage activity by methylation outside its recognition sequence.

The recombinant plasmid pGEM4Z-ras DNA which was methylated on dam and dcm sites outside the PvuII recognition sequence was digested with restriction endonuclease PvuII, and one of the three PvuII sites was about 16-fold less efficient to cleave than either of the other two. On the contrary, the three PvuII sites were cleaved at about the same rate on the unmethylated DNA molecule. The results show that the cleavage inhibition of the methylated DNA on the certain PvuII site was caused by methylation outside the PvuII recognition sequence. Maybe a adjacent methylated dam site *A was responsible for the less efficient cleavage. This observation suggests that methylation outside the recognition sequence may be considered a new factor in the kinetic experiment of restriction endonuclease.

Base Sequence↗

PubMed1990

Fuzzy adaptive least squares and its use in quantitative structure-activity relationships.

Fuzzy adaptive least squares (FALS), a pattern recognition method designed to correlate molecular structure with activity rating, has been developed. A novel feature of FALS is that the degree to which each sample belongs to an activity class is given using a membership function. The algorithm involves an iterative modification of forcing factors to maximize the sum of the membership function values over all samples. This paper first describes the method and calculation procedure of FALS89 (1989 version of FALS), and then shows its application to the correlation of structure with a potency rating of anticarcinogenic mitomycin derivatives and arginine-vasopressin antagonists. FALS89 applied to these samples showed considerably high reliability in both recognition and leave-one-out prediction.

Antibiotics, Antineoplastic↗