Moonlighting proteins in cancer

Abstract

Since the 1980s, growing evidence suggested that the cellular localization of proteins determined their activity and biological functions. In a classical view, a protein is characterized by the single cellular compartment where it primarily resides and functions. It is now believed that when proteins appear in different subcellular locations, the cells surpass the expected activity of proteins given the same genomic information to fulfill complex biological behavior. Many proteins are recognized for having the potential to exist in multiple locations in cells. Dysregulation of translocation may cause cancer or contribute to poorer cancer prognosis. Thus, quantitative and comprehensive assessment of dynamic proteins and associated protein movements could be a promising indicator in determining cancer prognosis and efficiency of cancer treatment and therapy. This review will summarize these so-called moonlighting proteins, in terms of a coupled intracellular cancer signaling pathway. Determination of the detailed biological intracellular and extracellular transit and regulatory activity of moonlighting proteins permits a better understanding of cancer and identification of potential means of molecular intervention.

Immunoproteomic and mass spectrometric analysis of Eimeria acervulina antigens recognized by antisera from chickens infected with E. acervulina, E. tenella or E. necatrix

“…The other five proteins in the same group had little information available, and thus, it is difficult to estimate their potential as vaccine candidates. However, based on the reported findings that many nuclear or intracellular proteins are "moonlighting" on the cell surface or being secreted to the outside of the cells, the proteins common to all three Eimeria species that stimulated antibody responses should be considered potential vaccine targets [45,46]. Ongoing Table 1 Immunoproteomic and mass-spectrometric identification of Eimeria acervulina sporozoite proteins recognized by immune sera of the three Eimeria species studied a Protein spot numbering in the 2-DE gel; spots 22 and 23 that had no detectable protein signals are not listed b Accession number in NCBI c Number of peptides that match the predicted protein sequence d Protein score is − 10*Log(P), where P is the probability that the observed match is a random event.…”

Cannabis: A Prehistoric Remedy for the Deficits of Existing and Emerging Anticancer Therapies

“…Apart from change in cellular localization, the functions of such moonlighting proteins can vary based on changes in redox state of cell, oligomeric state of the protein, and temperature or variations in cellular concentration of a substrate, ligand, cofactor or product. 111 The target proteins of different cancers have been identified as moonlighting proteins owing to their ability to accomplish mechanistically discrete functions.…”

On the move: Redox –dependent protein relocation

“…However, the number and diversity of proteins that either can have different 62 functions in the same intracellular compartment or that can move from one compartment to 63 another to fulfil different functions has increased enormously in recent years, aided by 64 development and application of bioinformatic (Chapple et al, 2015) proteomic (Thul et al, 65 2017) and cell imaging techniques (Chong et al, 2015;Thul et al, 2017). These reveal the 66 extent to which proteins can show multiple subcellular localisations (up to 50% of cellular 67 proteins), as well as how these may change in response to cellular perturbation (Chong et al, 68 2015), including in disease states like cancer in animals (Min et al, 2016) and stress 69 responses in plants (Sun et al 2018) . Several metabolic enzymes are known to move into the 70 nucleus affecting epigenetic modifications (Boukouris et al, 2016) and histone expression 71 (He et al, 2013) providing a link between metabolism and gene expression.…”