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Table 1 List of contextual determinants of nucleocytoplasmic shuttling with determination of opposite cancerous functions of cargos

From: PSPC1 is a new contextual determinant of aberrant subcellular translocation of oncogenes in tumor progression

Molecular determinant Shuttling protein Nuclear function of shuttling protein Mechanisms of nuclear shuttling protein Cytoplasmic function of shuttling protein Mechanisms of cytoplasmic shuttling protein Potential inhibitor Biomarker
PTK6 PTK6 is a tumor suppressor PTK6 is phosphorylated and trapped by PSPC1 PTK6 is an oncogene PTK6 interacts with proteins in oncogene networks PSPC1-CT131 Decreased PSPC1-pY523 expression predicts HCC tumor progression
[29, 30]
PML PML is a tumor suppressor TGIF1 sequesters cPML and acts as a negative TGF-β signal regulator Cytoplasmic PML (cPML) is an oncogene cPML is exported into the cytoplasm to interact with Smads for activating TGF-β pathway Arsenic trioxide (ATO) or All-trans-retinoic acid (ATRA) PML–RARα fusion oncogene in acute promyelocytic leukemia (APL)
[31, 32]
HEXIM1 HEXIM1 is a tumor suppressor P-TEFb sequesters HEXIM1, resulting in the inactivation of P-TEFb-mediated inhibition of RNA polymerase II transcription Cytoplasmic NPM mutant (NPMc+) is an oncogene NPMc + associates with and sequesters HEXIM1, leading to higher RNA polymerase II transcription Cytotoxic peptide of the basic region (BR) of HEXIM1 NPMc + is the signature for acute myeloid leukemia (AML)
P53 P53 is a tumor suppressor P53 acts as a suppressor to participate in DNA repair, apoptosis, and cell cycle progression P53 accumulation and retention in the cytoplasm lead to drug resistance and oncogenic features Cytoplasmic p53 is sequestered by mortalin due to p53 excessive nuclear export, low cytoplasmic degradation, and retention by the cytoskeleton. P53 peptide (323–337 amino acids), MKT-077, shRNAs of mortalin Cytoplasmic p53 is associated with poor chemotherapy, metastasis, and poor patient survival
[36, 37]
EBP50 is an oncogene EBP50/β-catenin enters the nucleus to stabilize β-catenin/TCF-1 to activate aberrant Wnt signaling EBP50 is a tumor suppressor EBP50 interacts with the PTEN tumor suppressor to attenuate PDGF receptor signaling siEBP50 Nuclear expression of EBP50 is associated with poor survival