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Biomedical subjects

M C Lien

Publications and source records attributed to M C Lien.

4 recordsLinked to original sources

Multiple spatial correspondence effects on dual-task performance.

Three dual-task experiments were conducted to examine whether the underadditive interaction of the Simon effect and stimulus onset asynchrony (SOA) on Task 2 performance is due to decay. The experiments tested whether the reverse Simon effect obtained with an incompatible stimulus-response (S-R) mapping would show an overadditive interaction with SOA, as predicted by R. De Jong, C.-C. Liang, and E. Lauber's (1994) dual-process model. Tone or letter identification tasks with vocal or keypress responses were used as Task 1. Task 2 was keypresses to arrow direction (or letter identity in Experiment 1). For all experiments, the normal Simon effect showed an underadditive interaction with SOA, but the reverse Simon effect did not show an overadditive interaction. The results imply that the dual-process model is not applicable to the dual-task context. Multiple correspondence effects across tasks implicate an explanation in terms of automatic S-R translation.

Adult↗

Aberrant regulation and function of wild-type p53 in radioresistant melanoma cells.

Sporadic human tumors and the hereditary cancer predisposition syndrome Li-Fraumeni are frequently associated with mutations in the p53 tumor suppressor gene that compromise its ability to function as a DNA damage checkpoint. A subset of Li-Fraumeni patients with wild-type p53 alleles have mutations in chk2/hcds1, one of the genes signaling the presence of DNA damage to the p53 protein. This suggests that p53 may be kept inactive in human cancer by mutations targeting DNA damage signaling pathways. Melanoma cells are highly radioresistant, yet they express wild-type p53 protein, raising the possibility of defects in the pathways that activate p53 in response to DNA damage. We have described a chk2/hcds1-independent DNA damage signaling pathway that targets Ser-376 within the COOH terminus of p53 for dephosphorylation and leads to increased p53 functional activity. We now report that in several human melanoma cell lines that express wild-type p53, the phosphorylation state of Ser-376 was not regulated by DNA damage. In these cell lines, neither the endogenous wild-type p53 protein nor high levels of ectopic wild-type p53 led to cell cycle arrest or apoptosis. Thus, defective activation of p53 in response to DNA damage may underlie the radioresistance of human melanoma cells.

14-3-3 Proteins↗

CREB-binding protein and p300/CBP-associated factor are transcriptional coactivators of the p53 tumor suppressor protein.

The structurally related transcriptional coactivators p300 and CBP possess histone acetyltransferase activity and associate with P/CAF, which is also a histone acetyltransferase. CBP and p300 have properties of tumor suppressor proteins; their interaction with P/CAF is disrupted by the adenoviral E1A oncoprotein, and the genes encoding CBP and p300 are mutated in human cancer. We observed a physical interaction between the transactivation domain of the p53 tumor suppressor protein and CBP. Furthermore, CBP and P/CAF enhanced the ability of p53 to activate expression of the endogenous p21(cip1/waf1) gene, whereas E1A and dominant negative CBP mutants suppressed p53-dependent p21(cip1/waf1) expression. These studies link two tumor suppressor families and provide a framework for understanding the molecular mechanism by which p53 activates transcription.

Binding Sites↗

Word frequency effects at brief exposure durations: comment on Paap and Johansen (1994).

K. R. Paap and L. S. Johansen (1994) proposed that word frequency effects do not occur on a lexical decision task (LDT) when postmasked target exposure duration is sufficiently brief because such a task prevents verification--their hypothesized locus of the word frequency effect. In making this assertion, they proposed that the activation interpretation of A. R. Dobbs, A. Friedman, and J. Lloyd (1985) and of P. A. Allen, M. McNeal, and D. Kvak (1992) was flawed. However, evidence that Paap and Johansen's conclusions were wrong and that their experimental design contained flaws is provided here. In Experiment 1 of the present study, word frequency effects were evident on an LDT at the 75% accuracy level proposed by Paap and Johansen as being sufficiently low to prevent verification. In Experiment 2 the mental lexica of participants from the same population as that used for Experiment 1 contained very-low-frequency words. Thus, the present results are consistent with an activation locus.

Analysis of Variance↗