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Updated: Mar 28, 2026

Reconstitution of Msp1 Extraction Activity with Fully Purified Components
Published on: August 10, 2021
Transmembrane domain is crucial to the subcellular localization and function of Myc target 1
Shuai Wu1, Jinghua Gui1, Xiaofei Yin1
1State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Abstract:
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 (MYCT1) is a direct target gene of c-MYC, and its murine homologue MT-MC1 recapitulated multiple c-Myc-related phenotypes. However, the molecular mechanism of MYCT1 remains unclear. Here, we identified the transmembrane (TM) domain of MYCT1, not the nuclear localization sequence, is indispensable to the vesicle-associated localization of MYCT1 protein in the cytoplasmic membrane vesicle. Overexpression of MYCT1, not MYCT1 (ΔTM), decreased cell viability under serum deprivation and increased tumour cell migration ability. We further identified CKAP4 interacted with MYCT1 and contributed to the function of MYCT1. 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 MYCT1.
Insights
The transmembrane domain of MYC target 1 (MYCT1) protein is crucial for its cellular localization and function in cancer. This domain regulates cell viability and migration, impacting cancer progression.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Deregulation of c-MYC is common in human cancers, promoting tumor growth and instability.
- MYC target 1 (MYCT1) is a direct c-MYC target gene, but its molecular mechanism is not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanism of MYCT1 and its role in cancer.
Main Methods:
- Investigated the role of MYCT1's transmembrane (TM) domain in protein localization using deletion mutants.
- Assessed the impact of MYCT1 overexpression on cell viability and migration.
- Identified interacting proteins using co-immunoprecipitation.
Main Results:
- The TM domain, not the nuclear localization sequence, is essential for MYCT1's localization to cytoplasmic membrane vesicles.
- Overexpression of MYCT1, dependent on its TM domain, reduced cell viability under serum deprivation and enhanced tumor cell migration.
- CKAP4 was identified as an interacting protein that contributes to MYCT1 function.
- A patient-derived mutation (A88D) in the TM domain disrupted localization and abolished functional effects.
Conclusions:
- The TM domain of MYCT1 is critical for its proper localization and function in regulating cell viability and migration.
- MYCT1's interaction with CKAP4 and its TM domain-mediated functions are important in the context of cancer.
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