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.

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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