Nuclear import of NLS- RARα is mediated by importin α/β

Ye, Jiao; Liu, Zhong; Xiong, Likuan; Li, Jian; Yu, Lihua; Dan, Wenran; Yuan, Zhen; Yao, Juanjuan; Zhong, Pengqiang; Liu, Junmei; Liu, Dongdong; Liu, Beizhong

doi:10.1016/j.cellsig.2020.109567

Cited by 8 publications

(4 citation statements)

References 35 publications

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“…PML/RARa, the hallmark fusion protein of acute promyelocytic leukemia, undergoes cleavage to generate an NLS bearing truncated RARα (NLS-RARα). NLS-RARα is recognized and transported to the nucleus, by the IPOα/IPOβ complex [ 90 ], where it promotes proliferation and inhibit differentiation of leukemia cells [ 91 ]. Similarly, in t (8;21- AML-1/ETO) AML, ETO bears a NLS sequence that is recognized by IPOα/β complex and mediates ETO and AML-1/ETO import into the nucleus [ 92 ].…”

Section: Key Pathways Regulated By Nuclear Import and Their Significamentioning

confidence: 99%

Targeting nuclear import and export in hematological malignancies

Nachmias

Schimmer

2020

Leukemia

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The transport of proteins across the nuclear membrane is a highly regulated process, essential for the cell function. This transport is actively mediated by members of the karyopherin family, termed importins, or exportins, depending on the direction of transport. These proteins play an active part in tumorigenesis, through aberrant localization of their cargoes, which include oncogenes, tumor-suppressor genes and mediators of key signal transduction pathways. Overexpression of importins and exportins is reported in many malignancies, with implications in cell growth and viability, differentiation, drug resistance, and tumor microenvironment. Given their broad significance across tumors and pathways, much effort is being put to develop specific inhibitors as a novel anticancer therapeutics. Already, selinexor, a specific inhibitor of exportin-1 (XPO1), is approved for clinical use. This review will focus on the role of importins and exportins in hematological malignancies. We will discuss current preclinical and clinical data on importins and exportins, and demonstrate how our growing understanding of their functions has identified new therapeutic targets.

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Section: Key Pathways Regulated By Nuclear Import and Their Significamentioning

confidence: 99%

Targeting nuclear import and export in hematological malignancies

Nachmias

Schimmer

2020

Leukemia

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“…However, they can work cooperatively to promote nuclear localization of MSX1, leading to a significant nuclear accumulation of the corresponding GFP fusion protein. Similarly, the promyelocytic leukemia-retinoic acid receptor α (PML/RARα) has two primary NLS, which include one from the PML ( 159 R N KKKK 164 ), and the other from the RARα ( 486 RK V IK 490 ), the NLS of the RARα portion in NLS-RARα is more favorable for the nuclear localization of NLS-RARα [ 33 , 45 ].…”

Section: Introductionmentioning

confidence: 99%

Types of nuclear localization signals and mechanisms of protein import into the nucleus

et al. 2021

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Nuclear localization signals (NLS) are generally short peptides that act as a signal fragment that mediates the transport of proteins from the cytoplasm into the nucleus. This NLS-dependent protein recognition, a process necessary for cargo proteins to pass the nuclear envelope through the nuclear pore complex, is facilitated by members of the importin superfamily. Here, we summarized the types of NLS, focused on the recently reported related proteins containing nuclear localization signals, and briefly summarized some mechanisms that do not depend on nuclear localization signals into the nucleus.

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“…KPNA2, an adaptor protein for nuclear receptor importinβ, mediates numerous nuclear translocations of macromolecules by classical nuclear localization signal through the nuclear pore complex. [25][26][27] KPNA2 has been first described in matched ductal carcinoma in situ (DCIS) and invasive lesions of the breast. 28 Furthermore, KPNA2 may be the primary determinant for transcription factors transporting and transcriptional activity in various cancers including breast cancer, melanoma, liver cancer, and lung cancer, and therefore is probably related to the cancer cell growth and invasion.…”

Section: Discussionmentioning

confidence: 99%

<p>Analyses of DNA Methylation Involved in the Activation of Nuclear Karyopherin Alpha 2 Leading to Identify the Progression and Prognostic Significance Across Human Breast Cancer</p>

Cui

Xuan²,

et al. 2020

CMAR

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Background: Karyopherin alpha 2 (KPNA2) is a nuclear import factor that plays a crucial role in nucleocytoplasmic transport, as well as cell proliferation, migration, and invasion in several cancers. However, the roles of KPNA2 in breast cancer as well as the underlying molecular mechanisms have not been elucidated. Materials and Methods: To evaluate gene expression alterations during breast carcinogenesis, KPNA2 expression was analyzed using the Gene Expression Profiling Interactive Analysis and Oncomine analyses. The correlation between methylation and expression was analyzed using the MEXPRESS tool, UALCAN cancer database, and cBioPortal browser. Then, the expression and prognostic value of KPNA2 were investigated by our own breast cancer samples using RT-PCR. KPNA2 methylation level was detected by methylationspecific PCR. Results: We obtained the following important results. (1) KPNA2 expression was significantly higher in breast cancer than normal samples and regulated by aberrant DNA hypomethylation of promoter region. (2) Among patients with breast cancer, those with higher KPNA2 expression had a lower survival rate. (3) The major mutation type of KPNA2 in breast cancer samples was missense mutation. (4) Homer1 was able to promote breast cancer progression may be through upregulating TPX2 expression. Conclusion: Our findings suggest that aberrant DNA hypomethylation of promoter regions contributes to the aberrant expression of KPNA2 in breast cancer, which might be a potential indicator of poor prognosis.

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Nuclear import of NLS- RARα is mediated by importin α/β

Cited by 8 publications

References 35 publications

Targeting nuclear import and export in hematological malignancies

Targeting nuclear import and export in hematological malignancies

Types of nuclear localization signals and mechanisms of protein import into the nucleus

<p>Analyses of DNA Methylation Involved in the Activation of Nuclear Karyopherin Alpha 2 Leading to Identify the Progression and Prognostic Significance Across Human Breast Cancer</p>

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