ERLIN2 Membrane Protein Introduction

Introduction of ERLIN2

ERLIN2 is encoded by the ERLIN2 gene and is also known as Endoplasmic reticulum lipid raft-associated protein 2 (ERLIN2), SPFH2 or C8ORF2. ERLIN2 is an endoplasmic reticulum (ER) membrane protein containing an evolutionarily conserved stomatin/prohibitin/flotillin/HflK/C (SPFH) domain. The ERLIN2 gene resides on chromosome 8p11.2, a region that is frequently found altered in human breast cancer and several childhood onset autosomal recessive motor neuron diseases, suggesting that ERLIN2 is critically involved in both tumor development and childhood motor neuron degeneration.

Function of ERLIN2 Membrane Protein

ERLIN2 is so far the first-identified ER protein that simultaneously interacts with spindle microtubules and Cyclin B1/CDK1 to regulate the cell division cycle. ERLIN2 is also the first identified SPFH domain-containing protein that regulates cell cycle through interacting with both microtubules and cyclin proteins. As an ER-associated MAP, ERLIN2 simultaneously interacts with α-tubulin, Cyclin B1 and Cdk1 during M phase. Importantly, through the interactions, ERLIN2 promotes K63-linked Cyclin B1 ubiquitination, thus stabilizing Cyclin B1 complex by preventing proteasome-mediated Cyclin B1 degradation. The interactions between ERLIN2 and Cyclin B1 are mediated through the SPFH domain of ERLIN2 protein. ERLIN2 likely associates rapidly with Cyclin B1 during G2/M phase and may act as a ‘recognition factor’ that selects Cyclin B1 to be ubiquitinated at specifically exposed lysine residues. Moreover, ERLIN2 also plays an important role in neuronal disease because the developmentally regulated expression and neuron-specific distribution of ERLIN2 in CNS are consistent with the neurological clinical symptoms of human neuronal disease caused by ERLIN2 mutations.

Fig.1 Schematic working model for the regulation of cell cycle progression by ERLIN2 (Zhang, 2015).

Application of ERLIN2 Membrane Protein in Literature

1. Zhang X., et al. A novel ER–microtubule-binding protein, ERLIN2, stabilizes Cyclin B1 and regulates cell cycle progression. Cell Discovery. 2015, 1:15024. PubMed ID: 27462423
   
   

   Authors in this article identify a novel ER-microtubule-binding protein, ERLIN2. More importantly, ERLIN2 interacts with and stabilizes mitosis-promoting factors to regulate cell cycle progression associated with human breast cancer malignancy.

2. Wu H., et al. MiR-410 Acts as a Tumor Suppressor in Estrogen Receptor-Positive Breast Cancer Cells by Directly Targeting ERLIN2 via the ERS Pathway. Cell Physiol Biochem. 2018, 48(2):461-474. PubMed ID: 30016800
   
   

   The results of this article indicate that miR-410 suppresses cell growth, migration, and invasion by directly down-regulating ERLIN2 in ER positive breast cancer, acting as a tumor suppressor.

3. Wang G., et al. Endoplasmic reticulum factor ERLIN2 regulates cytosolic lipid content in cancer cells. The Biochemical journal. 2012, 446(3):415-425. PubMed ID: 22690709
   
   

   The article identifies that ERLIN2 is a regulator of cytosolic lipid content in cancer cells and has important implications for understanding the molecular basis of tumorigenesis and the treatment of cancer.

4. Wang G., et al. ERLIN2 promotes breast cancer cell survival by modulating endoplasmic reticulum stress pathways. BMC Cancer. 2012, 12:225-225. PubMed ID: 22681620
   
   

   This article suggests that ERLIN2 may be involved in the growth of breast cancer cells by facilitating a cytoprotective response to various cellular stresses associated with oncogenesis.

5. Rydning S.L., et al. A novel heterozygous variant in ERLIN2 causes autosomal dominant pure hereditary spastic paraplegia. European Journal of Neurology. 2018, 25(7):943-e971. PubMed ID: 29528531
   
   

   This article reports that biallelic variants in ERLIN2 are known to cause recessive hereditary spastic paraplegias type SPG18 and ERLIN2 variants should also be considered in the diagnostic evaluation of patients with autosomal dominant hereditary spastic paraplegias.

ERLIN2 Preparation Options

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Reference

1. Zhang X., et al. (2015) A novel ER–microtubule-binding protein, ERLIN2, stabilizes Cyclin B1 and regulates cell cycle progression. Cell Discovery. 1:15024.

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