title: A novel ER-microtubule-binding protein, ERLIN2, stabilizes Cyclin B1 and regulates cell cycle progression.
abstract: The gene encoding endoplasmic reticulum (ER) lipid raft-associated protein 2 (ERLIN2) is amplified in human breast cancers. ERLIN2 gene mutations were also found to be associated with human childhood progressive motor neuron diseases. Yet, an understanding of the physiological function and mechanism for ERLIN2 remains elusive. In this study, we reveal that ERLIN2 is a spatially and temporally regulated ER-microtubule-binding protein that has an important role in cell cycle progression by interacting with and stabilizing the mitosis-promoting factors. Whereas ERLIN2 is highly expressed in aggressive human breast cancers, during normal development ERLIN2 is expressed at the postnatal stage and becomes undetectable in adulthood. ERLIN2 interacts with the microtubule component α-tubulin, and this interaction is maximal during the cell cycle G2/M phase where ERLIN2 simultaneously interacts with the mitosis-promoting complex Cyclin B1/Cdk1. ERLIN2 facilitates K63-linked ubiquitination and stabilization of Cyclin B1 protein in G2/M phase. Downregulation of ERLIN2 results in cell cycle arrest, represses breast cancer proliferation and malignancy and increases sensitivity of breast cancer cells to anticancer drugs. In summary, our study revealed a novel ER-microtubule-binding protein, ERLIN2, which interacts with and stabilizes mitosis-promoting factors to regulate cell cycle progression associated with human breast cancer malignancy.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine , Detroit, MI, USA.
authors.forename: Xuebao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine , Detroit, MI, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Cai
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine , Detroit, MI, USA.
authors.forename: Ze
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA; Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Polin
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine , Chicago, IL, USA.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine , Detroit, MI, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Dandekar
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA; Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Physiology, Wayne State University School of Medicine , Chicago, IL, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA; Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Russell L
authors.initials: RL
authors.lastname: Finley
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Deyu
authors.initials: D
authors.lastname: Fang
authors.affiliation: Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA; Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Zeng-Quan
authors.initials: ZQ
authors.lastname: Yang
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA; Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA; Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Kezhong
authors.initials: K
authors.lastname: Zhang
keywords: Cyclin B1; ER lipid raft protein; breast cancer; endoplasmic reticulum; microtubule; mitosis