Cofilin-1 and Other ADF/Cofilin Superfamily Members in Human Malignant Cells.

Sergey Shishkin,Natalya Pashintseva,Lidia Eremina,Leonid Kovalev,Marina Kovaleva

doi:10.3390/ijms18010010

Sergey Shishkin, Natalya Pashintseva + Show 3 more

Open Access

https://doi.org/10.3390/ijms18010010

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Abstract

Identification of actin-depolymerizing factor homology (ADF-H) domains in the structures of several related proteins led first to the formation of the ADF/cofilin family, which then expanded to the ADF/cofilin superfamily. This superfamily includes the well-studied cofilin-1 (Cfl-1) and about a dozen different human proteins that interact directly or indirectly with the actin cytoskeleton, provide its remodeling, and alter cell motility. According to some data, Cfl-1 is contained in various human malignant cells (HMCs) and is involved in the formation of malignant properties, including invasiveness, metastatic potential, and resistance to chemotherapeutic drugs. The presence of other ADF/cofilin superfamily proteins in HMCs and their involvement in the regulation of cell motility were discovered with the use of various OMICS technologies. In our review, we discuss the results of the study of Cfl-1 and other ADF/cofilin superfamily proteins, which may be of interest for solving different problems of molecular oncology, as well as for the prospects of further investigations of these proteins in HMCs.

Highlights

The key features of malignant neoplasms include uncontrolled proliferation, as well as the ability to invade surrounding tissues and to spread locally and regionally or even to distant parts of the body
We discuss the results of the study of Cfl-1 and other ADF/cofilin superfamily proteins, which may be of interest for solving different problems of molecular oncology, as well as for the prospects of further investigations of these proteins in human malignant cells (HMCs)
These features are the basis for ideas about the common origin of malignant tumors from stem cells [1,2] and for revealing typical patterns that are associated with tumor phenotypes [3], in particular, by using different OMICS technologies [4]

Summary

Introduction

The key features of malignant neoplasms include uncontrolled proliferation, as well as the ability to invade surrounding tissues (invasion) and to spread locally and regionally or even to distant parts of the body (metastasis). Classification of ADF/cofilin superfamily members relies on their structural (amino acid sequences, ADF-H domains) and functional (actin binding) features. Unlike Lappalainen et al [29], Nakano et al [40] described the group of GMF-family members (GMF-G can bind F-actin) and did not include coactosin and coactosin-like proteins, which only bind to F-actin, in the group of ADF/cofilins (that bind to both F- and G-actin and promote actin depolymerization). Drebrins and Abp1s have a single ADF-H domain in their N-termini, followed by a nonconserved central region and a C-terminal region These proteins have been shown to bind F-actin and stabilize actin filaments. The fifth, separate, group includes coactosin from D. discoideum and coactosin-like proteins (from different species including that of H. sapiens—UniProt Q14019) These proteins are entirely composed of a single ADF-H domain and have a MW (about 17 kDa) similar to the MW of traditional cofilins. F-actin (actin stabilization), cyclin-dependent kinase 5, connexin 43 and other proteins

Biological Functions

Regulaton

Conclusions

Findings

30. PDBsum