Open AccessTransmembrane domain is crucial to the subcellular localization and function of Myc target 1
Author(s) -
Wu Shuai,
Gui Jinghua,
Yin Xiaofei,
Pan Qiang,
Liu Xinyuan,
Chu Liang
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12747
Subject(s) - transmembrane protein , subcellular localization , biology , microbiology and biotechnology , nuclear localization sequence , cell growth , transmembrane domain , viability assay , cytoplasm , cell , apoptosis , mutation , phenotype , gene , genetics , receptor
Deregulation of c‐ MYC occurs in a variety of human cancers. Overexpression of c‐ MYC promotes cell growth, proliferation, apoptosis, transformation and genomic instability. MYC target 1 ( MYCT 1) is a direct target gene of c‐ MYC , and its murine homologue MT ‐ MC 1 recapitulated multiple c‐Myc‐related phenotypes. However, the molecular mechanism of MYCT 1 remains unclear. Here, we identified the transmembrane ( TM ) domain of MYCT 1, not the nuclear localization sequence, is indispensable to the vesicle‐associated localization of MYCT 1 protein in the cytoplasmic membrane vesicle. Overexpression of MYCT 1, not MYCT 1 (Δ TM ), decreased cell viability under serum deprivation and increased tumour cell migration ability. We further identified CKAP 4 interacted with MYCT 1 and contributed to the function of MYCT 1. In addition, we found that a mutation, A88D, which is observed in patient sample, changed the localization, and abolished the effect on cell viability and cell migration, suggesting that the TM domain is critical to MYCT 1.