14-3-3 Proteins Are on the Crossroads of Cancer, Aging, and Age-Related Neurodegenerative Disease

Fan, Xiaolan; Cui, Lang; Zeng, Yao; Song, Wenhao; Gaur, Uma; Yang, Mingyao

doi:10.3390/ijms20143518

Cited by 86 publications

(70 citation statements)

References 136 publications

(102 reference statements)

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“… 28 Nevertheless, as outlined in Table 1 , there is convincing experimental evidence for both tissue-specific distribution of isoforms and isoform-specific functions. 29 − 38 The extent to which these differences contribute to the pharmacology of FC is unknown. Therefore, as part of a program to develop FC variants with enhanced selectivity profiles, we analyzed the isoform-specificity profile of FC in vitro .…”

Section: Introductionmentioning

confidence: 99%

Probing the 14-3-3 Isoform-Specificity Profile of Protein–Protein Interactions Stabilized by Fusicoccin A

et al. 2020

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Fusicoccin A (FC) is a fungal phytotoxin that stabilizes protein–protein interactions (PPIs) between 14-3-3 adapter proteins and their phosphoprotein interaction partners. Recently, FC has emerged as an important chemical probe of human 14-3-3 PPIs involved in cancer and neurobiology. These previous studies have established the structural requirements for FC-induced stabilization of 14-3-3·client phosphoprotein complexes; however, the effect of 14-3-3 isoforms on FC activity remains underexplored. This is a relevant question for the continued development of FC variants because there are seven isoforms of 14-3-3 in humans. Despite their sequence and structural similarities, a growing body of experimental evidence supports both tissue-specific expression of 14-3-3 isoforms and isoform-specific functions in vivo . Herein, we interrogate the isoform-specificity profile of FC in vitro using recombinant 14-3-3 isoforms and a library of fluorescein-labeled hexaphosphopeptides mimicking the C-terminal recognition domains of client proteins that are characterized targets of FC in vivo . Our results reveal modest isoform preferences for individual client phospholigands and demonstrate that FC differentially stabilizes PPIs involving 14-3-3σ. Together, these data support the feasibility of developing FC variants with enhanced isoform selectivity.

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Section: Introductionmentioning

confidence: 99%

Probing the 14-3-3 Isoform-Specificity Profile of Protein–Protein Interactions Stabilized by Fusicoccin A

et al. 2020

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“…They are conserved proteins in all eukaryotic cells, and play chaperon role in protein correct folding. 14-3-3 proteins are considered to be at the crossroad between aging and cancer as they have shown consistent expression patterns in these two conditions [24]. Therefore, care should be taken when analyzing 14-3-3 epsilon as proteomic biomarker in Ssc patients, and adjustments for patient's age should be taken under consideration.…”

Section: Discussionmentioning

confidence: 99%

Candidate proteomic biomarkers in systemic sclerosis discovered using mass-spectrometry: an update of a systematic review (2014–2020)

Bălănescu

Balanescu

Bălănescu

et al. 2021

Romanian Journal of Internal Medicine

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Background: Systemic sclerosis (Ssc) is an autoimmune disease characterized by graduate cutaneous and tissue fibrosis development and irreversible fibroproliferative vascular changes. The aim of the current systematic review was to update the list of proteomic candidate biomarkers identified from Ssc samples with mass spectrometry techniques.Methods: Medline and Scopus databases were searched on 1st September 2020. Relevant articles were searched from March 2014 until September 2020. Two independent reviewers evaluated the retrieved articles.Results: From a total of 97 articles, 9 articles were included in the final analysis summarizing 539 candidate proteomic biomarkers from various samples from Ssc patients (a larger number compared to the previous systematic review). Most biomarkers were identified from cutaneous biopsies. Only 5 articles included a validation step of the findings with only 13 biomarkers being validated.Conclusions: Although many candidate biomarkers were additionally identified, independent validation studies are needed in order to evaluate the importance of these biomarkers for Ssc patients.

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“…For example, 14-3-3 protein beta/alpha (1433B) plays important roles in cancer signaling. Collectively, the 14-3-3 proteins are considered tumor suppressors, whose down-regulation has been frequently detected in tumor specimens of many types of cancer [36].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Colon Cancer Tissues: Discovery of New Candidate Biomarkers

Buttacavoli

Albanese²,

Roz

et al. 2020

IJMS

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Colon cancer is an aggressive tumor form with a poor prognosis. This study reports a comparative proteomic analysis performed by using two-dimensional differential in-gel electrophoresis (2D-DIGE) between 26 pooled colon cancer surgical tissues and adjacent non-tumoral tissues, to identify potential target proteins correlated with carcinogenesis. The DAVID functional classification tool revealed that most of the differentially regulated proteins, acting both intracellularly and extracellularly, concur across multiple cancer steps. The identified protein classes include proteins involved in cell proliferation, apoptosis, metabolic pathways, oxidative stress, cell motility, Ras signal transduction, and cytoskeleton. Interestingly, networks and pathways analysis showed that the identified proteins could be biologically inter-connected to the tumor-host microenvironment, including innate immune response, platelet and neutrophil degranulation, and hemostasis. Finally, transgelin (TAGL), here identified for the first time with four different protein species, collectively down-regulated in colon cancer tissues, emerged as a top-ranked biomarker for colorectal cancer (CRC). In conclusion, our findings revealed a different proteomic profiling in colon cancer tissues characterized by the deregulation of specific pathways involved in hallmarks of cancer. All of these proteins may represent promising novel colon cancer biomarkers and potential therapeutic targets, if validated in larger cohorts of patients.

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14-3-3 Proteins Are on the Crossroads of Cancer, Aging, and Age-Related Neurodegenerative Disease

Cited by 86 publications

References 136 publications

Probing the 14-3-3 Isoform-Specificity Profile of Protein–Protein Interactions Stabilized by Fusicoccin A

Probing the 14-3-3 Isoform-Specificity Profile of Protein–Protein Interactions Stabilized by Fusicoccin A

Candidate proteomic biomarkers in systemic sclerosis discovered using mass-spectrometry: an update of a systematic review (2014–2020)

Proteomic Profiling of Colon Cancer Tissues: Discovery of New Candidate Biomarkers

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