Insulin-Like Growth Factor Binding Protein-3 Binds to Histone 3.

Apurva Bhardwaj,Shailly Varma Shrivastav,Kumar Alok Pathak,Anuraag Shrivastav

doi:10.3390/ijms22010407

Abstract

Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) is an essential protein that regulates cellular processes such as cell proliferation, apoptosis, and differentiation. It is known to bind with several proteins to carry out various cellular functions. In this study, we report for the first time that IGFBP-3 is a histone 3 (H3) binding protein. Sub-cellular fractionation was performed to separate into cytosolic fraction, nucleic acid binding protein fraction and insoluble nuclear fraction. Using ligand blot analysis, we identified a ~15 kDa protein that can interact with IGFBP-3 in the insoluble nuclear fraction. The 15 kDa protein was confirmed as histone 3 by far-Western blot analysis and co-immunoprecipitation experiments. A dot-blot experiment further validated the binding of IGFBP-3 with H3. The intensity of IGFBP-3 on dot-blot showed a proportional increase with H3 concentrations between 2.33 pmol–37.42 pmol. Our results support the presence of protein-protein interaction between IGFBP-3 and H3. The physical binding between IGFBP-3 and H3 could indicate its yet another cellular role in regulating the chromatin remodeling for gene transcription.

Highlights

Insulin-like growth factor binding protein 3 (IGFBP-3) is an essential protein involved in regulating various cellular processes, including cell proliferation, apoptosis, cell survival and differentiation [1]
We were interested investigating binding partners the nuNuclear IGFBP-3 is known to play a role in gene transcription and DNA repair
We have demonstrated that IGFBP-3 protein can bind with histone 3 (H3) protein

Summary

Introduction

Insulin-like growth factor binding protein 3 (IGFBP-3) is an essential protein involved in regulating various cellular processes, including cell proliferation, apoptosis, cell survival and differentiation [1]. The delivery of insulin like growth factors (IGF) produced primarily by the liver cells to the target cells via the bloodstream is a well-established endocrine function of IGFBP-3. IGFBP-3 can function in an IGF-dependent as well in an IGF-independent manner. The IGF-dependent primary function of IGFBP-3 is to transport IGFs sequestered within the ternary complex to the IGF receptors (IGFRs) for the initiation of a cascade of downstream signaling events. The IGF-independent roles of IGFBP-3 are elicited by internalization through various endocytic mechanisms, and translocation into the nucleus to interact with intracellular proteins

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Conclusion