S100A6 binds p53 and affects its activity

Słomnicki, Łukasz P.; Nawrot, Barbara; Leśniak, Wiesława

doi:10.1016/j.biocel.2008.08.007

Cited by 109 publications

(89 citation statements)

References 36 publications

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“…47 In this context, interactions with tumor associated proteins such as annexin A2 and p53 may indicate a role of S100-A6 in cancer progression and metastasis. 48,49 Indeed, increased levels of S100-A6 have been found to be associated with metastasis or survival in colon and pancreatic cancer, respectively. 50,51 Similarly, our study showed a significant correlation of S100-A6 expression with clinical parameters such as regional lymph node metastasis, distant metastasis, tumor cell differentiation, and prognosis.…”

Section: Discussionmentioning

confidence: 99%

MALDI Imaging Identifies Prognostic Seven-Protein Signature of Novel Tissue Markers in Intestinal-Type Gastric Cancer

Balluff

Rauser

Meding

et al. 2011

The American Journal of Pathology

127

109

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Proteomics-based approaches allow us to investigate the biology of cancer beyond genomic initiatives. We used histology-based matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry to identify proteins that predict disease outcome in gastric cancer after surgical resection. A total of 181 intestinal-type primary resected gastric cancer tissues from two independent patient cohorts were analyzed. Protein profiles of the discovery cohort (n ‫؍‬ 63) were directly obtained from tumor tissue sections by MALDI imaging. A seven-protein signature was associated with an unfavorable overall survival independent of major clinical covariates. The prognostic significance of three individual proteins identified (CRIP1, HNP-1, and S100-A6) was validated immunohistochemically on tissue microarrays of an independent validation cohort (n ‫؍‬ 118). Whereas HNP-1 and S100-A6 were found to further subdivide early-stage (Union Internationale Contre le Cancer [UICC]-I) and late-stage (UICC II and III) cancer patients into different prognostic groups, CRIP1, a protein previously unknown in gastric cancer, was confirmed as a novel and independent prognostic factor for all patients in the validation cohort. The protein pattern described here serves as a new independent indicator of patient survival complementing the previously known clinical parameters in terms of prognostic relevance. These results show that this tissue-based proteomic approach may provide clinically relevant information that might be beneficial in improving risk stratification for gastric cancer patients.

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Section: Discussionmentioning

confidence: 99%

MALDI Imaging Identifies Prognostic Seven-Protein Signature of Novel Tissue Markers in Intestinal-Type Gastric Cancer

Balluff

Rauser

Meding

et al. 2011

The American Journal of Pathology

127

109

View full text Add to dashboard Cite

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“…The interactions of S100 proteins with p63 and p73 are likely to be physiologically relevant. The interaction of several S100 proteins with p53 has been firmly established in vitro and in vivo in several studies (Baudier et al, 1992;Scotto et al, 1998Scotto et al, , 1999Grigorian et al, 2001;Lin et al, 2001Lin et al, , 2004Fernandez-Fernandez et al, 2005, 2008Mueller et al, 2005;Slomnicki et al, 2009;van Dieck et al, 2009). It is, therefore, reasonable to assume that the interactions with the paralogs p63 and p73 also occur in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, a subset of the protein family binds to the negative regulatory domain (367-393) of the tumor suppressor. Further, S100 proteins have been shown to potentially activate as well as inhibit p53 (Baudier et al, 1992;Scotto et al, 1998Scotto et al, , 1999Rustandi et al, 2000;Grigorian et al, 2001;Lin et al, 2001Lin et al, , 2004Fernandez-Fernandez et al, 2005, 2008Mueller et al, 2005;Salama et al, 2008;Slomnicki et al, 2009;van Dieck et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Molecular basis of S100 proteins interacting with the p53 homologs p63 and p73

et al. 2010

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S100 proteins modulate p53 activity by interacting with its tetramerization (p53TET, residues 325-355) and transactivation (residues 1-57) domains. In this study, we characterized biophysically the binding of S100A1, S100A2, S100A4, S100A6 and S100B to homologous domains of p63 and p73 in vitro by fluorescence anisotropy, analytical ultracentrifugation and analytical gel filtration. We found that S100A1, S100A2, S100A4, S100A6 and S100B proteins bound different p63 and p73 tetramerization domain variants and naturally occurring isoforms with varying affinities in a calcium-dependent manner. Additional interactions were observed with peptides derived from the p63 and p73 N-terminal transactivation domains. Importantly, S100 proteins bound p63 and p73 with different affinities in their different oligomeric states, similarly to the differential modes of binding to p53. On the basis of our data, we hypothesize that S100 proteins regulate the oligomerization state of all three p53 family members and their isoforms, with a potential physiological relevance in developmental and disease-related processes. The regulation of the p53 family by S100 is complicated and depends on the target preference of each individual S100 protein, the concentration of the proteins and calcium, as well as the splicing variation of p63 or p73. Our results outlining the complexity of the interaction should be considered when studying the functional effects of S100 proteins in their biological context.

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“…However, we have noticed that the clone formation efficiency was lower in ADAR1-knockdown H9 cells than that in control cells (Supplementary information, Figure S1F). RNA-seq and RT-qPCR results further revealed that some key pro-apoptotic genes, such as S100A6 and BAX [31][32][33], were upregulated and the anti-apoptotic gene SFRP1 [34,35] was downregulated in ADAR1-knockdown H9 cells (Supplementary information, Figure S1G and Table S2), suggesting that ADAR1 deficiency can promote apoptosis of hESCs under certain stresses, such as enzymatic detachment. This is consistent with a previous report that cells cultured from ADAR1-deficient embryos exhibited increased apoptosis when a stress response was induced [24].…”

Section: Adar1 Knockdown Has Little Effect On Hesc Pluripotencymentioning

confidence: 98%

ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner

et al. 2015

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Adenosine deaminases acting on RNA (ADARs) are involved in adenosine-to-inosine RNA editing and are implicated in development and diseases. Here we observed that ADAR1 deficiency in human embryonic stem cells (hESCs) significantly affected hESC differentiation and neural induction with widespread changes in mRNA and miRNA expression, including upregulation of self-renewal-related miRNAs, such as miR302s. Global editing analyses revealed that ADAR1 editing activity contributes little to the altered miRNA/mRNA expression in ADAR1-deficient hESCs upon neural induction. Genome-wide iCLIP studies identified that ADAR1 binds directly to pri-miRNAs to interfere with miRNA processing by acting as an RNA-binding protein. Importantly, aberrant expression of miRNAs and phenotypes observed in ADAR1-depleted hESCs upon neural differentiation could be reversed by an enzymatically inactive ADAR1 mutant, but not by the RNA-binding-null ADAR1 mutant. These findings reveal that ADAR1, but not its editing activity, is critical for hESC differentiation and neural induction by regulating miRNA biogenesis via direct RNA interaction.

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S100A6 binds p53 and affects its activity

Cited by 109 publications

References 36 publications

MALDI Imaging Identifies Prognostic Seven-Protein Signature of Novel Tissue Markers in Intestinal-Type Gastric Cancer

MALDI Imaging Identifies Prognostic Seven-Protein Signature of Novel Tissue Markers in Intestinal-Type Gastric Cancer

Molecular basis of S100 proteins interacting with the p53 homologs p63 and p73

ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner

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