Dataset Information

Good Cop, Bad Cop: Defining the Roles of ?40p53 in Cancer and Aging.

ABSTRACT: The tumour suppressor p53 is essential for maintaining DNA integrity, and plays a major role in cellular senescence and aging. Understanding the mechanisms that contribute to p53 dysfunction can uncover novel possibilities for improving cancer therapies and diagnosis, as well as cognitive decline associated with aging. In recent years, the complexity of p53 signalling has become increasingly apparent owing to the discovery of the p53 isoforms. These isoforms play important roles in regulating cell growth and turnover in response to different stressors, depending on the cellular context. In this review, we focus on ?40p53, an N-terminally truncated p53 isoform. ?40p53 can alter p53 target gene expression in both a positive and negative manner, modulating the biological outcome of p53 activation; it also functions independently of p53. Therefore, proper control of the ?40p53: p53 ratio is essential for normal cell growth, aging, and responses to cancer therapy. Defining the contexts and the mechanisms by which ?40p53 behaves as a "good cop or bad cop" is critical if we are to target this isoform therapeutically.

SUBMITTER: Steffens Reinhardt L

PROVIDER: S-EPMC7352174 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Good Cop, Bad Cop: Defining the Roles of Δ40p53 in Cancer and Aging.

Steffens Reinhardt Luiza L Zhang Xiajie X Wawruszak Anna A Groen Kira K De Iuliis Geoffry N GN Avery-Kiejda Kelly A KA

Cancers 20200623 6

The tumour suppressor p53 is essential for maintaining DNA integrity, and plays a major role in cellular senescence and aging. Understanding the mechanisms that contribute to p53 dysfunction can uncover novel possibilities for improving cancer therapies and diagnosis, as well as cognitive decline associated with aging. In recent years, the complexity of p53 signalling has become increasingly apparent owing to the discovery of the p53 isoforms. These isoforms play important roles in regulating ce ...[more]

PMID: 32585821

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Project description:Concealing the possession of relevant information represents a complex cognitive process, shaped by contextual demands and individual differences in cognitive and socio-emotional functioning. The Reaction Time-based Concealed Information Test (RT-CIT) is used to detect concealed knowledge based on the difference in RTs between denying recognition of critical (probes) and newly encountered (irrelevant) information. Several research questions were addressed in this scenario implemented after a mock crime. First, we were interested whether the introduction of a social stimulus (facial identity) simulating a virtual investigator would facilitate the process of deception detection. Next, we explored whether his emotional displays (friendly, hostile or neutral) would have a differential impact on speed of responses to probe versus irrelevant items. We also compared the impact of introducing similar stimuli in a working memory (WM) updating context without requirements to conceal information. Finally, we explored the association between deceptive behavior and individual differences in WM updating proficiency or in internalizing problems (state / trait anxiety and depression). Results indicated that the mere presence of a neutral virtual investigator slowed down participants' responses, but not the appended lie-specific time (difference between probes and irrelevants). Emotional expression was shown to differentially affect speed of responses to critical items, with positive displays from the virtual examiner enhancing lie-specific time, compared to negative facial expressions, which had an opposite impact. This valence-specific effect was not visible in the WM updating context. Higher levels of trait / state anxiety were related to faster responses to probes in the negative condition (hostile facial expression) of the RT-CIT. These preliminary findings further emphasize the need to take into account motivational and emotional factors when considering the transfer of deception detection techniques from the laboratory to real-life settings.

Dataset Information

Good Cop, Bad Cop: Defining the Roles of ?40p53 in Cancer and Aging.

Publications

Good Cop, Bad Cop: Defining the Roles of Δ40p53 in Cancer and Aging.

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