Transmembrane domain is crucial to the subcellular localization and function of Myc target 1

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.

Dual role of endothelial Myct1 in tumor angiogenesis and tumor immunity

“…3L). A similar binding pattern between MYCT1 and CKAP4 in HEK293T cells was also reported in a previous study (35). Because ZO1 plays a critical role in EC functions such as barrier formation, tension, and migration (36) and RHOA regulates endothelial tight junction maintenance and barrier formation in close association with ZO1 (37), we investigated whether there is a functional interplay between MYCT1, ZO1, and RHOA through a series of combined KD and overexpression of these genes in MCEC cells.…”

“…Mouse MYCT1 protein shares an 85% sequence identity with the human MYCT1 protein (fig. S11A) (30,35). To determine whether MYCT1 function is conserved between human and mouse, we knocked down human MYCT1 in HUVEC (human umbilical vein endothelial cell) (HUVEC hMKD) cells (fig.…”

Comparative analysis of FKBP family protein: evaluation, structure, and function in mammals and Drosophila melanogaster

“…This implies that CG1847 could be involved in cell cycle-associated transcription and istargeted on both mitosis and sensory physiology [ 7 , 23 , 24 ]. Furthermore, CG5482 is reported to be a Myc target gene and its expression is directly regulated by dMyc ( Drosophila Myc) in larva [ 25 , 26 ]. Furthermore, c-MYC regulates over 15% of genomic genes through binding to the consensus sequence—termed E-boxes in mammal cells.…”

Identifying Candidate Genes Involved in the Regulation of Early Growth Using Full-Length Transcriptome and RNA-Seq Analyses of Frontal and Parietal Bones and Vertebral Bones in Bighead Carp (Hypophthalmichthys nobilis)

“…In addition to the genes of energy metabolism and immune function, cytoskeletal genes have been identified as candidate growth-related genes in fish ( Salem et al, 2012 ). In this study, we found a differential expression of cytoskeletal genes such as myc target protein 1 homolog ( myct1 ), Golgi apparatus protein 1 ( glg1 ), zinc finger protein 574 ( znf574 ), and actin filament–associated protein 1-like 2 ( afap1l2 ) in the two groups with different growth rates ( Mourelatos et al, 1995 ; Berg et al, 2010 ; Tie et al, 2016 ; Wu et al, 2016 ), suggesting that they play important roles in cell growth, proliferation, apoptosis, and transformation. The protein tyrosine phosphatase 4A (PTP4A) family, consisting of PTP4A1/PRL1, PTP4A2/PRL2, and PTP4A3/PRL3, has been implicated in cell proliferation and tumorigenesis ( Kobayashi et al, 2014 ).…”

“…Among the aforementioned DEGs ( Figure 6 ), several DEGs have been identified as candidate genes regulating growth in previous transcriptomic and genomic studies, including scd , ube4b , atp1b , myct1 , b2m , and mhcII ( Xu et al, 2013 ; Wu et al, 2016 ; Lu et al, 2019 ; Zhou et al, 2019 ). These reports provide additional support to our findings of these genes being significantly involved in the modulation of differential growth in different domestic animals.…”