Biomedical subjects

C Wilson Xu

Publications and source records attributed to C Wilson Xu.

3 recordsLinked to original sources

PubMed2002

Inactivation of Ras function by allele-specific peptide aptamers.

One challenge facing biology is the elucidation of the function of the estimated 30 000 human genes and their polymorphic variants. Reagents that affect the activity of specific genes will be useful in the dissection of cellular regulatory networks. Here, as a test case, we used a two-bait two-hybrid system to identify peptide aptamers that distinguish allelic forms of H-Ras. Some of these anti-Ras aptamters inhibit the interaction of oncogenic Ras with c-Raf1 in vitro, and abolish EGF-stimulated activation of c-Raf1 in vivo. These experiments show that the inactivation of protein function by peptide aptamers represents a viable approach to the understanding and control of signaling pathways and oncogenic missense alleles.

Alleles↗

PubMed2002

Activation of p53 by protein inhibitor of activated Stat1 (PIAS1).

The tumor suppressor protein p53 functions as a transcriptional factor that activates genes controlling cell cycle arrest and apoptosis. Here, we report that protein inhibitor of activated Stat1 (PIAS1) interacts with the tetramerization and C-terminal regulatory domains of p53 in yeast two-hybrid analyses. Endogenous PIAS1 is also associated with endogenous p53 in mammalian cells. Ectopic expression of PIAS1 activates p53-mediated expression in mouse embryonic fibroblast cells (p53(-/-)) as well as a variety of other cell lines. Furthermore, ectopic expression of PIAS1 induces p53-mediated expression of cyclin-dependent kinase inhibitor p21 and G(1) arrest of the cell cycle in H1299 cells. In addition, a PIAS1 mutant without the RING-finger domain required for sumoylation could still activate p53-mediated gene expression, indicating that activation of p53 by PIAS1 does not require the RING-finger domain. Taken together, our results suggest that PIAS1 is a novel activator of p53.

Adenosine Triphosphate↗

PubMed2002

High-density cell microarrays for parallel functional determinations.

Whole-genome sequencing projects have generated a wealth of gene sequences from a variety of organisms. A major challenge is to rapidly uncover gene regulatory circuits and their functional manifestations at the cellular level. Here we report the coupled fabrication of nanocraters ranging in size from 100 pL to 1.5 nL on permeable membranes for culturing cells. Using this approach, we developed bacterial and yeast cell microarrays that allowed phenotypic determinations of gene activities and drug targets on a large scale. Cell microarrays will therefore be a particularly useful tool for studying phenotypes of gene activities on a genome-wide scale.

Bacteriological Techniques↗