Table 1.

Tumor-suppressor proteins, cell-cycle inhibitors, transcription factors, and drug targets that undergo XPO1-mediated nuclear export

ProteinRoleBrief description of functionTumors in which XPO-mediated nuclear export may be functionally relevant
p53Tumor suppressorGuardian of the genome: induces cell-cycle arrest, activates DNA repair proteins to maintain genomic integrity and, if necessary, initiates apoptosis following DNA damage.Colorectal, breast, and ovarian cancer, retinoblastomas, and neuroblastoma
APCTumor suppressorInhibits WNT signaling by targeting β-catenin for proteasome-mediated degradation in the cytoplasm.Colorectal cancer
Activating transcription factor 2 (ATF2)Transcription factorsMember of the leucine zipper family of transcription factors that regulates transcription of genes involved in antiapoptosis, cell growth, and DNA damage response.Melanoma, prostate cancer
BCR–ABLTyrosine kinaseConstitutively active BCR–ABL tyrosine kinase. Caused by reciprocal translocation between chromosomes 9 and 22, t(9;22)(q34;q11), resulting in the formation of the BCR–ABL fusion gene.CML
Bcl2-related ovarian killer protein (BOK)Proapoptotic proteinExerts proapoptotic function through the mitochondrial pathway.Breast and cervical cancer cell lines
BRCA1Tumor suppressorRegulates the DNA damage response and repair functions in the nucleus and at centrosomes to inhibit centrosome duplication after DNA damage.Breast cancer
CIP2AOncogenic proteinInhibits protein PP2A and stabilizes the oncogenic transcription factor c-Myc.Head and neck and colon cancer
CDK inhibitor 1 (p21, CIP1)Cell-cycle inhibitorRegulates cell-cycle progression from G1-phase by inhibiting the activity of cyclin-CDK2 or cyclin-CDK1 complexes.Ovarian and breast cancer and CML
CDK inhibitor 1B (p27, KIP1)Cell-cycle inhibitorInhibits cyclin E/CDK2, thus blocking G1–S phase transition.Ovarian, esophageal, thyroid, colon, and breast carcinomas
ERKOncogenic proteinCytoplasmic localization of activated ERK1/2 is required for its antiapoptotic activity.Melanoma
ER-αPrevents S-phase entryNuclear export of ER-α into the cytoplasm is required for estradiol-dependent activation of DNA synthesis and entry into S-phase of the cell cycle.Breast cancer
FOXO transcription factors (FOXO1, FOXO3a, FOXO4 and FOXO6)Tumor suppressorNegative regulators of cell proliferation, cell survival, and cell-cycle progression.Breast, prostate, and thyroid cancer, glioblastoma, and melanoma
Galectin-3Regulator of proliferation/apoptosisMultifunctional protein that regulates cell proliferation and can induce apoptosis in cancer cells.Thyroid, prostate, and breast cancer
HSP90Molecular chaperoneHSP90 chaperone machinery is required to prevent mutated and overexpressed oncoproteins from misfolding and degradation in cancer cells.Breast cancer
InI1/hSNF5Tumor suppressorComponent of the chromatin remodeling SWI/SNF complex whose tumor-suppressor functions include inducing G1 arrest and controlling the mitotic spindle checkpoint. Deleted in malignant rhabdoid tumors.Malignant rhabdoid tumors
Moesin–ezrin–radixin-like protein (Merlin/NF2)Tumor suppressorNeurofibromatosis type 2 (NF2) gene encodes the tumor-suppressor protein Merlin, which is an ERM (ezrin, radixin, and moesin) protein family member that regulates proliferation, apoptosis, survival, motility, adhesion, and invasion.Inherited schwannomas, meningiomas, and ependymomas
Nucleophosmin (NPM)Tumor suppressorCentrosome-associated protein with aberrant cytoplasmic expression observed in several hematologic malignancies.AML and breast cancer
Neuronal Wiskott–Aldrich syndrome protein (N-WASP)/focal adhesion kinase (FAK)Regulators of actin cytoskeletonPhosphorylation of FAK leads to phosphorylation of N-WASP, which promotes cell motility and invasion.Neural Wiskott–Aldrich syndrome, breast, esophageal, and ovarian cancer
Ras association domain-containing protein 2 (RASSF2)Tumor suppressorBinds KRAS with the characteristics of an effector and promotes apoptosis and cell-cycle arrest.Thyroid cancer, nasopharyngeal carcinoma
Retinoblastoma (RB1)Tumor suppressorInhibits G1–S phase transition of the cell cycle in response to DNA damage.Retinoblastoma
RUNX3Tumor suppressorAssociated with transforming growth factor-β signaling and functions as a tumor suppressor in gastric carcinogenesis. Suppresses the development of colon cancer by forming a complex with β-catenin-TCF4 and attenuating WNT-mediated signaling activity.Breast, colon, and gastric cancer
SurvivinInhibitor of apoptosisMember of inhibitor-of-apoptosis protein family (IAP) that exerts its cytoprotective effects when located in the cytoplasm by inhibiting apoptotic pathways.Breast cancer, oral, and oropharyngeal squamous cell carcinoma
Transducer of ErbB-2 (TOB)Tumor suppressorCell-cycle inhibitor that induces arrest at G1–S phase, upregulates cyclin-dependent kinase inhibitor p27, and downregulates the antiapoptotic proteins Bcl-2 and Bcl-XLBreast cancer
Topoisomerase IRelaxation of supercoiled DNAEnzyme that catalyzes the relaxation of supercoiled DNA during replication, transcription, recombination, and chromosome condensation. Cellular target of camptothecin.Anaplastic astrocytoma and neuroblastomas
Topoisomerase IIαRelaxation of supercoiled DNAEnzyme that catalyzes the relaxation of supercoiled DNA during replication, transcription, recombination, and chromosome condensation. Cellular target of doxorubicn and etoposide.Multiple myeloma
Vitamin D3 upregulated protein 1 (VDUP1)Tumor suppressorMediates nuclear export of the hypoxia-inducible factor-1α (HIF-1α), a transcriptional activator of angiogenesis, anaerobic metabolism, and survival pathways, leading to proteasomal degradation of HIF-1α in the cytoplasm.Cervical and lung cancer cell lines
WEE1Tumor suppressorInhibitor of CDK1 and key molecule in maintaining G2 cell-cycle checkpoint arrest for premitotic DNA repair.Currently unknown—but reduced expression of WEE1 has been observed in non–small cell lung, colon, and prostate cancer