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W B Solomon

Publications and source records attributed to W B Solomon.

9 recordsLinked to original sources
PubMed2000

A novel glutamine-rich putative transcriptional adaptor protein (TIG-1), preferentially expressed in placental and bone-marrow tissues.

We used a subtractive hybridization protocol to identify novel expressed sequence tags (ESTs) corresponding to mRNAs whose expression was induced upon exposure of the human leukemia cell line K562 to the phorbol ester 12-O-tetradecanolyphorbol-13-acetate (TPA). The complete open reading frame of one of the novel ESTs, named TIG-1, was obtained by screening K562 cell and placental cDNA libraries. The deduced open reading frame of the TIG-1 cDNA encodes for a glutamine repeat-rich protein with a predicted molecular weight of 63kDa. The predicted open reading frame also contains a consensus bipartite nuclear localization signal, though no specific DNA-binding domain is found. The corresponding TIG-1 mRNA is ubiquitously expressed. Placental tissue expresses the TIG-1 mRNA 200 times more than the lowest expressing tissues such as kidney and lung. There is also preferential TIG-1 mRNA expression in cells of bone-marrow lineage.In-vitro transcription/translation of the TIG-1 cDNA yielded a polypeptide with an apparent molecular weight of 97kDa. Using polyclonal antibodies obtained from a rabbit immunized with the carboxy-terminal portion of bacterially expressed TIG-1 protein, a polypeptide with molecular weight of 97kDa was identified by Western blot analyses of protein lysates obtained from K562 cells. Cotransfection assays of K562 cells, using a GAL4-TIG-1 fusion gene and GAL4 operator-CAT, indicate that the TIG-1 protein may have transcriptional regulatory activity when tethered to DNA. We hypothesize that this novel glutamine-rich protein participates in a protein complex that regulates gene transcription. It has been demonstrated by Naar et al. (Naar, A.M., Beaurang, P.A., Zhou, S., Abraham, S., Solomon, W.B., Tjian, R., 1999, Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature 398, 828-830) that the amino acid sequences of peptide fragments obtained from a polypeptide found in a complex of proteins that alters chromatin structure (ARC) are identical to portions of the deduced open reading frame of TIG-1 mRNA.

Amino Acid Sequence↗
PubMed1996

Schistosoma mansoni: effect of recombinant tumor necrosis factor alpha on fecundity and [14C]-tyrosine uptake in females maintained in vitro.

It has been reported that recombinant tumor necrosis factor alpha (rTNF alpha) stimulates egg-laying in Schistosoma mansoni females. Because tyrosine requirement is increased in female undergoing sexual maturation in preparation for oogenesis and tyrosine is a major component of eggshell protein, we wanted to determine whether females treated with rTNF alpha would also incorporate more tyrosine. Adult females were first treated with 10, 20 or 40 ng/ml rTNF alpha for 1, 3 or 6 hr in RPMI 1640 containing 10% fetal calf serum (FCS). Another two groups of females were each exposed either to males or to male excretory-secretory (ES) products for 1 hr. They were then exposed to 20 microCi/ml-1 [14C]-tyrosine for 1 hr in RPMI 1640 containing 10% FCS. All females were incubated individually unless indicated otherwise. Females incorporated more tyrosine after exposure to males or their ES products. They incorporated significantly more tyrosine when treated with rTNF alpha for 1 hr; the increased uptake correlated with increasing amounts of rTNF alpha used. Although after a 3-hr treatment with 10 ng/ml rTNF alpha females incorporated slightly more tyrosine than controls, increasing amounts of rTNF alpha had an adverse effect. Females treated with rTNF alpha for 6 hr incorporated less tyrosine than controls and those treated for 1 hr. SDS-PAGE and fluorography did not reveal any differences in polypeptide profiles of untreated and rTNF alpha-treated females. These unexpected results led us to study the effect of rTNF alpha on fecundity in females. Contrary to the published report, we observed a sharp decline in egg-laying in females when exposed to increasing concentrations of rTNF alpha in vitro.

Animals↗
PubMed1994

Iron protoporphyrin IX (hemin) but not tin or zinc protoporphyrin IX can stimulate gene expression in K562 cells from enhancer elements containing binding sites for NF-E2.

Many genes whose transcription is erythroid-specific contain enhancer or promoter elements that bind the transcription factor NF-E2. Hemin induction increases the expression of globin genes in the human erythroleukemia cell line K562, and increases the expression of reporters gene regulated by an enhancer elements containing binding sites for NF-E2. The failure of metalloporphyrins other than hemin to stimulate the transient expression of a CAT reporter gene linked to an enhancer element containing a binding site for NF-E2 was correlated with their failure to induce benzidine-positive K562 cells and increase the steady-state level of gamma-globin mRNA. This study suggests that elevated levels of zinc protoporphyrin IX found in the anemia of chronic disease, iron deficiency, and lead poisoning may contribute to a decrease in globin gene expression by interfering with the transcriptional activity of enhancer elements containing binding sites for NF-E2.

Base Sequence↗
PubMed1994

Phorbol ester induction of differentiation and apoptosis in the K562 cell line is accompanied by marked decreases in the stability of globin mRNAs and decreases in the steady state level of mRNAs encoding for ribosomal proteins L35, L31, L27, and L21.

To understand how phorbol ester induction switches the leukemia cell line K562 from erythroid specific gene expression to an apparently irreversible program of megakaryocytic gene expression, we used a subtractive cDNA cloning strategy to identify cDNA sequence tags whose expression was suppressed after exposure of K562 cells to phorbol ester. The switch from the erythroid to megakaryocytic phenotype of K562 cells is due, at least in part, to marked decreases in the half-lives of erythroid specific mRNAs. The phorbol ester induced decreases in the half-lives of erythroid specific mRNAs is reversed by cycloheximide or an inhibitor of protein kinase C. The phorbol ester induced shut off of cell division, and apparent terminal differentiation and apoptosis of K562 cells is also associated with a coordinate decrease in the expression of mRNAs that encode ribosomal proteins.

Apoptosis↗
PubMed1994

Do questions about lead exposure predict elevated lead levels?

OBJECTIVE: To assess the usefulness of the lead poisoning questionnaire developed by the Centers for Disease Control and Prevention as a screening tool for elevated lead levels. METHODS: This descriptive study used a five-question questionnaire at our hospital-based general pediatric clinic and in two local private practices. We obtained venous lead levels from 485 children aged 9 months to 6 years who were brought for health supervision visits. The questionnaire was completed by a primary caretaker of 330 patients (68%). Contingency tables were used to compare lead levels with the responses on the questionnaire. RESULTS: Lead levels of > or = 10 micrograms/dL were found in 23 (7%) of 330 who completed the questionnaire. Caretakers of children with elevated lead levels were more likely to answer yes to questions about chipping paint and home remodeling than those whose children had levels < 10 (P = .0001). These questions had sensitivities for detecting elevated lead levels of 70% and 74% with negative predictive values of 97% and 98%, respectively. Questions about known contacts with lead poisoning and job or industrial exposure to lead each had sensitivities of < 10%. The Centers for Disease Control and Prevention's definition of high risk for lead poisoning (one or more positive responses) was nearly 90% sensitive for detecting elevated lead levels with a negative predictive value of 99%. CONCLUSION: This risk assessment questionnaire is an effective screening method for elevated lead levels in our population. Questions about the home environment were more sensitive indicators of elevated lead levels than other standard high-risk questions.

Centers for Disease Control and Prevention, U.S.↗
PubMed1993

Suppression of a cellular differentiation program by phorbol esters coincides with inhibition of binding of a cell-specific transcription factor (NF-E2) to an enhancer element required for expression of an erythroid-specific gene.

Induction by hemin increases, while induction with 12-O-tetradecanoylphorbol-13-acetate (TPA) represses, erythroid-specific gene expression in the human cell line K562. We analyzed the effects of hemin or TPA induction on the binding and activity of transcription factors at a regulatory element found within the transcriptional regulatory sequences of many erythroid-specific genes. TPA induction increases the binding of ubiquitous AP-1 factors to this element. TPA induction inhibits the binding of the lineage limited transcription factor NF-E2 to this transcriptional control element. Hemin induction of K562 cells does not facilitate the binding of NF-E2 to its recognition site. Hemin induction appears to nonspecifically increase the expression of transiently transfected genes in K562 cells. Beyond this nonspecific increase in gene expression, hemin induction acts to increase the activity of the lineage limited transcription factor NF-E2. The divergent effects of hemin and TPA on gene expression in K562 cells are mediated, in part, by their contrasting effects on the transcription factor NF-E2.

Base Sequence↗
PubMed1991

Association of nm23-H1 allelic deletions with distant metastases in colorectal carcinoma.

A prospective study analysed the prognostic value of nm23-H1 allelic deletions in colorectal cancer. Of 21 patients with no evidence of distant metastases at initial operation, 11 showed nm23-H1 allelic deletions (including 1 homozygous deletion); 10 had no nm23-H1 deletions. After median follow-up of 25 months, distant metastases had developed in 8 of 11 (73%) patients with nm23-H1 deletions but in only 2 of 10 (20%) without nm23-H1 deletions (p less than 0.03). Tests with probe YNZ 22.1, near p53, showed no significant association with distant metastases. nm23-H1 may be, or may be located near, a late-acting suppressor gene in colorectal carcinoma, in which deletions may have prognostic value.

Aged↗
PubMed1989

An erythroid-specific, developmental-stage-independent enhancer far upstream of the human "beta-like globin" genes.

We have identified an erythroid-specific enhancer element far upstream of the human "beta-like globin" genes, at 10.2-11.0 kilobases 5' of the embryonic epsilon-globin gene, and thus at 53-54 kilobases 5' of the adult beta-globin gene. It is capable of enhancing the expression of a cis-linked test gene by up to 300-fold. This enhancer element is apparently developmental-stage-independent, as it is functional at the embryonic and the adult developmental stages in erythroid cells that are expressing the respective beta-like globin genes. The enhancer and globin promoter sequences work in synergy and are capable of conferring on a cis-linked gene the high transcriptional efficiency (enhancer function), erythroid specificity (enhancer and promoter functions), and developmental-stage specificity (promoter function) that are characteristic of the in vivo transcription of the beta-like globin genes in erythroid cells.

Age Factors↗