Open Access

REVIEW

A hypothesis for a novel role of RIN1-the modulation of telomerase function by the MAPK signaling pathway

by PATRIC HAMBLETON, MANUEL ALEJANDRO BARBIERI

1 Department of Biological Sciences, Florida International University, Miami, 33199, USA
2 Biomedical Science Institute, Florida International University, Miami, 33199, USA
3 Fairchild Tropical Botanic Garden, Miami, 33156, USA
4 International Center of Tropical Botany, Florida International University, Miami, FL, 33199, USA

* Address correspondence to: Manuel Alejandro Barbieri,

BIOCELL 2020, 44(4), 525-534. https://doi.org/10.32604/biocell.2020.011407

Received 07 May 2020; Accepted 13 August 2020; Issue published 24 December 2020

Abstract

Cancerous cells display abnormalities in the signal transduction pathways responsible for responding to extracellular growth factors, or mitogens. Mutations that alter proteins involved in these types of pathways can lead to inappropriate or unregulated cell growth, and therefore predispose the cell to become malignant. The critical role of the Ras/mitogen-activated protein kinase (MAPK) pathway in transducing growth signals to the interior of the cell and subsequently stimulating cell growth and proliferation is underscored by the fact that roughly one quarter of all human tumors contain mutant forms of Ras proteins. A particular focus on the signaling and membrane trafficking adaptor protein known as Ras interference 1 (RIN1) will reveal how this protein can potentially play a significant role in the development of the cancerous phenotype in certain cell types. Of equal interest is the possible connection between the Ras/MAPK pathway, and subsequent expression and enzymatic activity of telomerase–a key enzyme known to be overexpressed in roughly 85% of all cancers. RIN1 is a 783 amino acid (84 kDa) cytosolic protein that is involved in key steps of growth factor receptormediated endocytosis and can potentially moderate signaling through the MAPK pathways. RIN1, with its unique ability to compete directly with Raf for activation by Ras, could potentially influence signaling through more than one of the MAPK pathways. If so, RIN1 may then be able to exert a precise and selective effect on the downstream signal(s) of a MAPK target such as telomerase.

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