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Resveratrol binds and activates RKIP protein in colorectal cancer

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Abstract

Raf-1 kinase inhibitory protein (RKIP) acts as a tumor cell metastasis suppressor and prognostic indicator for survival in various cancers. Its use is predicted to improve therapy for various malignancies, including colorectal cancer (CRC). RKIP, frequently denoted as phosphatidylethanolamine-binding protein 1, is expressed in all normal mammalian tissues. RKIP functions as an inhibitor of the Raf-1, PI-3K, and MAP kinase (MAPK) pathways. In this study, we found that resveratrol induced the expression of RKIP at protein levels. To elucidate the structural basis of the interaction between resveratrol and RKIP, we performed computational studies that explore the binding affinity and ligand efficacy of resveratrol against RKIP. This study reveals the prognostic significance of RKIP metastasis suppressor activity against CRC and its structural arrangements during drug–target interactions.

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Abbreviations

AA:

Amino acids

CASTp:

Computed Atlas of Surface Topography of Proteins

COX-2:

Cyclooxygenase-2

CRC:

Colorectal cancer

GPCR:

G protein-coupled receptor

GRK2:

G protein-coupled receptor kinases

HPV:

Human papillomavirus

iNOS:

Inducible nitric oxide synthase

MAPK:

Mitogen-activated protein kinases

MMP:

Matrix metalloproteinases

NF-κB:

Nuclear factor kappa B

PDB:

Protein Data Bank

PEBP1:

Phosphatidylethanolamine-binding protein

PGE2:

Prostaglandin E2

PKC:

Protein kinase C

PPARα:

Peroxisome proliferator-activated receptor α

ProSA:

Protein structure analysis

PTEN:

Phosphatase and tensin homolog

PTK:

Protein tyrosine kinase

pTyr:

Phospho tyrosine

QMEAN:

Qualitative model energy analysis

RCSB:

Research Collaboratory for Structural Bioinformatics

RKIP:

Raf-1 kinase inhibitory protein

SIRT1:

Sirtuin

SMILES:

Simplified molecular input line entry System

STAT:

Signal transducer and activators of transcription

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Bioscience and Biotechnology, Banasthali University, Vanasthali, Rajasthan, 304022, India

    Begum Dariya, Gowru Srivani & Afroz Alam

  2. Biomedical Informatics Centre, ICMR-Regional Medical Research Centre, Bhubaneswar, Odisha, 751 023, India

    Santosh Kumar Behera

  3. Department of Biotechnology, Jawaharlal Nehru Technological University, Hyderabad, Telangana, 500085, India

    Sheik Aliya

  4. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA

    Ganji Purnachandra Nagaraju

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  1. Begum Dariya
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  2. Santosh Kumar Behera
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  3. Gowru Srivani
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  4. Sheik Aliya
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  5. Afroz Alam
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  6. Ganji Purnachandra Nagaraju
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Contributions

Data processing: BD, SKB, GS, AA and GPN. Study design: BD, SA, AA and GPN. Experimental studies: BD, SKB, GS, GC, SA, and AA. Manuscript editing: BD, GS, GC, SA, AA and GPN.

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Correspondence to Ganji Purnachandra Nagaraju.

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Handling Editor: A. G. de Brevern.

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Dariya, B., Behera, S.K., Srivani, G. et al. Resveratrol binds and activates RKIP protein in colorectal cancer. Amino Acids 52, 1299–1306 (2020). https://doi.org/10.1007/s00726-020-02889-2

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  • DOI: https://doi.org/10.1007/s00726-020-02889-2

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