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Biomedical subjects

C Luckey

Publications and source records attributed to C Luckey.

6 recordsLinked to original sources
PubMed1997

High incidence of Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus in tumor lesions and peripheral blood mononuclear cells from patients with Kaposi's sarcoma in Uganda.

With the advent of AIDS, Kaposi's sarcoma (KS) has become one of the leading malignancies in sub-Saharan Africa. Recently, DNA sequences from a new human herpesvirus called KS-associated herpesvirus (KSHV) or human herpesvirus type 8 have been found in KS tumor lesions in high frequency. Analyses of tumor lesions from 38 Ugandan KS patients indicated a uniform presence of KSHV in KS tumor lesions as revealed by polymerase chain reaction and Southern hybridization. In contrast, only 31% (11/36) of the normal skin biopsies from the same patient population were positive. The frequency of KSHV DNA detection in peripheral blood mononuclear cells (PBMC) of KS patients was also high (84%, 31/37). Similar analyses revealed the presence of cytomegalovirus (21% in KS lesions) to be discordant with KS development. A large number of KS lesions (87%, 33/38) and KS PBMC (70%, 26/37) were, however, positive for Epstein-Barr virus sequences. In addition, KSHV DNA was not found in the PBMC of Ugandans without KS.

Adult↗
PubMed1993

Three peroxisome protein packaging pathways suggested by selective permeabilization of yeast mutants defective in peroxisome biogenesis.

We have identified five complementation groups of peroxisome biogenesis (peb) mutants in Saccharomyces cerevisiae by a positive selection procedure. Three of these contained morphologically recognizable peroxisomes, and two appeared to lack the organelle altogether. The packaging of peroxisomal proteins in these mutants has been analyzed with a new gentle cell fractionation procedure. It employs digitonin titration for the selective permeabilization of yeast plasma and intracellular membranes. Proteins were measured by enzymatic assay or by quantitative chemiluminescent immunoblotting. With this gentle fractionation method, it was demonstrated that two mutants are selectively defective in assembling proteins into peroxisomes. Peb1-1 packages catalase and acyl-CoA oxidase within peroxisomes but not thiolase. Peb5-1 packages thiolase and acyl-CoA oxidase within peroxisomes but not catalase. The data suggest that the peroxisome biogenesis machinery contains components that are specific for each of three classes of peroxisomal proteins, represented by catalase, thiolase, and acyl-CoA oxidase. In the two mutants lacking morphologically recognizable peroxisomes, peb2-1 and peb4-1, all three enzymes were mislocalized to the cytosol.

Acetyl-CoA C-Acetyltransferase↗
PubMed1992

Biological function of the retinoblastoma protein requires distinct domains for hyperphosphorylation and transcription factor binding.

Despite the importance of the retinoblastoma susceptibility gene to tumor growth control, the structural features of its encoded protein (pRb) and their relationship to protein function have not been well explored. We constructed a panel of deletion mutants of pRb expression vectors and used a biological assay for pRb that measures growth inhibition and morphologic changes in pRb-transfected Saos-2 cells to correlate structural alterations of the pRb coding region with function. We tested the deleted proteins for the ability to bind to viral oncoprotein E1A and to the transcription factor E2F. We also measured the ability of the mutant proteins to become hyperphosphorylated in vivo and to be recognized as substrates in vitro by a cell cycle-regulatory kinase associated with cyclin A. We identified two regions of pRb that are required for E2F binding and for hyperphosphorylation. E1A binding domains partially overlap but are distinct from both of these other two regions. Biological function of pRb is dependent on retention of the integrity of both of these biochemically defined domains. These data support the model that pRb is a transducer of afferent signals (via the kinase that phosphorylates it) and efferent signals (through transcription factor binding), using distinct structural elements. Preservation of both of these features is essential for the ability of pRb to induce growth inhibition and morphologic changes upon reintroduction into transfected cells.

Adenovirus E1A Proteins↗