Tumor suppressor BAP1 nuclear import is governed by transportin-1

Yang, Tzu-Jing; Li, Tian-Neng; Huang, Rih-Sheng; Pan, Max; Lin, Shu‐Yu; Lin, Steven; Wu, Kuen‐Phon; Wang, Lily; Hsu, Shang-Te Danny

doi:10.1083/jcb.202201094

Cited by 7 publications

(4 citation statements)

References 52 publications

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“…Similar to what is observed in TP53 germline mutations in the Li-Fraumeni syndrome, BAP1 germline mutations are inherited as autosomal-dominant mutations with high penetrance, since more than 80% of carriers are destined to develop at least one of the main BAP1 -associated malignancies throughout their life. Of note, the genomic analysis of BAP1 -related tumors has highlighted the loss of the remaining BAP1 wild-type allele, something that suggests the possible role as “two-hits” tumor suppressor gene by BAP1 [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Profile and Prognostic Value of BAP1 Mutations in Intrahepatic Cholangiocarcinoma: A Genomic Database Analysis

Rizzo

Carloni

Ricci

et al. 2022

JPM

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Background. Recent years have witnessed the advent of molecular profiling for intrahepatic cholangiocarcinoma (iCCA), and new techniques have led to the identification of several molecular alterations. Precision oncology approaches have been widely evaluated and are currently under assessment, as shown by the recent development of a wide range of agents targeting Fibroblast Growth Factor Receptor (FGFR) 2, Isocitrate Dehydrogenase 1 (IDH-1), and BRAF. However, several knowledge gaps persist in the understanding of the genomic landscape of this hepatobiliary malignancy. Methods. In the current study, we aimed to comprehensively analyze clinicopathological features of BAP1-mutated iCCA patients in public datasets to increase the current knowledge on the molecular and biological profile of iCCA. Results. The current database study, including 772 iCCAs, identified BAP1 mutations in 120 cases (15.7%). According to our analysis, no differences in terms of overall survival and relapse-free survival were observed between BAP1-mutated and BAP1 wild-type patients receiving radical surgery. In addition, IDH1, PBRM1, and ARID1A mutations were the most commonly co-altered genes in BAP1-mutated iCCAs. Conclusions. The genomic characterization of iCCA is destined to become increasingly important, and more efforts aimed to implement iCCA genomics analysis are warranted.

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Section: Introductionmentioning

confidence: 99%

Molecular Profile and Prognostic Value of BAP1 Mutations in Intrahepatic Cholangiocarcinoma: A Genomic Database Analysis

Rizzo

Carloni

Ricci

et al. 2022

JPM

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“…BAP1 is regulated by ubiquitination through the E2 ubiquitin-conjugating enzyme UBE2O, which results in its sequestration in the cytoplasm [ 71 ]. This is counteracted through TNPO1 binding [ 72 ]. Moreover, cBAP1 is reported to regulate processes via its cytoplasmic fraction, such as apoptosis via modulation of IP3R3-mediated ER Ca 2+ release [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Correlation between BAP1 Localization, Driver Mutations, and Patient Survival in Uveal Melanoma

Cole

Zhang

Gallo

et al. 2022

Cancers

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Uveal melanoma (UM) is an uncommon but highly aggressive ocular malignancy. Poor overall survival is associated with deleterious BAP1 alterations, which frequently occur with monosomy 3 (LOH3) and a characteristic gene expression profile. Tumor DNA from a cohort of 100 UM patients from Moorfields Biobank (UK) that had undergone enucleation were sequenced for known UM driver genes (BAP1, SF3B1, EIF1AX, GNAQ, and GNA11). Immunohistochemical staining of BAP1 and interphase FISH for chromosomes 3 and 8 was performed, and cellular localization of BAP1 was correlated with BAP1 mutations. Wildtype (WT) BAP1 staining was characterized by nBAP1 expression with <10% cytoplasmic BAP1 (cBAP1). Tumors exhibited heterogeneity with respect to BAP1 staining with different percentages of nBAP1 loss: ≥25% loss of nuclear BAP1 (nBAP1) was superior to chr8q and LOH3 as a prognostic indicator. Of the successfully sequenced UMs, 38% harbored oncogenic mutations in GNA11 and 48% harbored mutations in GNAQ at residues 209 or 183. Of the secondary drivers, 39% of mutations were in BAP1, 11% were in EIF1AX, and 20% were in the SF3B1 R625 hotspot. Most tumors with SF3B1 or EIF1AX mutations retained nuclear BAP1 (nBAP1). The majority of tumor samples with likely pathogenic BAP1 mutations, regardless of mutation class, displayed ≥25% loss of nBAP1. This included all tumors with truncating mutations and 80% of tumors with missense mutations. In addition, 60% of tumors with truncating mutations and 82% of tumors with missense mutations expressed >10% cBAP1.

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“…83 Furthermore, TNPO1 imports the Wnt signaling effector β-catenin as well as the tumor suppressor BAP1, and many viruses exploit TNPO1 for nuclear entry and replication. [104][105][106][107] Proteome analysis indicated that proteins related to nuclear division and tRNA ligases are preferentially cargoes of TNPO1, while proteins related to DNA repair and HMG proteins are preferentially imported by TNPO2. 88 Interestingly, TNPO2 enhances export of a large proportion of mRNAs through the formation of a complex with RanGTP and the mRNA export factor NXF1, 108 suggesting that it may be appropriate to classify TNPO2 as a biportin.…”

Section: Components Of the Nuclear Transport Systemmentioning

confidence: 99%

Nuclear transport proteins: structure, function, and disease relevance

Yang,

Guo,

Chen

et al. 2023

Sig Transduct Target Ther

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Proper subcellular localization is crucial for the functioning of biomacromolecules, including proteins and RNAs. Nuclear transport is a fundamental cellular process that regulates the localization of many macromolecules within the nuclear or cytoplasmic compartments. In humans, approximately 60 proteins are involved in nuclear transport, including nucleoporins that form membrane-embedded nuclear pore complexes, karyopherins that transport cargoes through these complexes, and Ran system proteins that ensure directed and rapid transport. Many of these nuclear transport proteins play additional and essential roles in mitosis, biomolecular condensation, and gene transcription. Dysregulation of nuclear transport is linked to major human diseases such as cancer, neurodegenerative diseases, and viral infections. Selinexor (KPT-330), an inhibitor targeting the nuclear export factor XPO1 (also known as CRM1), was approved in 2019 to treat two types of blood cancers, and dozens of clinical trials of are ongoing. This review summarizes approximately three decades of research data in this field but focuses on the structure and function of individual nuclear transport proteins from recent studies, providing a cutting-edge and holistic view on the role of nuclear transport proteins in health and disease. In-depth knowledge of this rapidly evolving field has the potential to bring new insights into fundamental biology, pathogenic mechanisms, and therapeutic approaches.

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Tumor suppressor BAP1 nuclear import is governed by transportin-1

Cited by 7 publications

References 52 publications

Molecular Profile and Prognostic Value of BAP1 Mutations in Intrahepatic Cholangiocarcinoma: A Genomic Database Analysis

Molecular Profile and Prognostic Value of BAP1 Mutations in Intrahepatic Cholangiocarcinoma: A Genomic Database Analysis

Correlation between BAP1 Localization, Driver Mutations, and Patient Survival in Uveal Melanoma

Nuclear transport proteins: structure, function, and disease relevance

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