Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nuclear export protein chromosome maintenance region 1, found to be elevated in non-Hodgkin's lymphomas, controls localization of critical tumor suppressor proteins. Nuclear localization of tumor suppressor proteins is necessary for their cell surveillance function. However, their nuclear exclusion by chromosome maintenance region 1 renders them ineffective making this nuclear transporter an attractive therapeutic target. We have identified selective inhibitors of nuclear export that lock tumor suppressor proteins in the cell nucleus leading to apoptosis of lymphoid but not normal cells. Our inhibitors induce tumor suppressor protein nuclear retention-dependent growth inhibition and apoptosis in a panel of non-Hodgkin's lymphoma cell lines. Western blot of nuclear protein fraction and confocal microscopy analysis demonstrated retention of major tumor suppressor proteins in the cell nucleus. Co-immunoprecipitation studies showed disruption of the tumor suppressor protein-chromosome maintenance region 1 interaction. Small inhibitor RNA knockdown of two major tumor suppressor proteins, p53 in wild-type protein-53 and protein 73 in mutant-protein-53, abrogated inhibitor activity. Oral administration of related inhibitor at 75 and 150 mg/kg resulted in 65 and 70% tumor reduction, respectively and subcutaneous injections of inhibitor (25 and 75 mg/kg) resulted in 70 and 74% suppression of non-Hodgkin's lymphoma tumor growth with no toxicity; residual tumors showed activation of the protein 73 pathway. Our study verifies chromosome maintenance region 1 as a therapeutic target in non-Hodgkin's lymphoma, indicating that this nuclear export protein warrants further clinical investigations.
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PMID:Selective inhibitors of nuclear export for the treatment of non-Hodgkin's lymphomas. 2400 15

LIM domains-containing protein 1 (LIMD1) is a tumor suppressor protein downregulated in numerous solid malignancies. However, the functional role of LIMD1 in non-Hodgkin's lymphoma (NHL) remains unclear. In the present study, it was demonstrated that LIMD1 is associated with the proliferation of NHL and cell adhesion mediated-drug resistance (CAM-DR). It was indicated by western blot analysis that LIMD1expression is lower in progressive lymphoma compared with indolent lymphoma. Furthermore, it was indicated that the role of LIMD1 in cell viability and proliferation remains unclear. Finally, the present study demonstrated that LIMD1 serves an important role in CAM-DR by regulating cell cycle progression. Silencing of LIMD1 may reverse CAM-DR in NHL. Therefore, the findings of the present study suggested that LIMD1 may be a potential therapeutic target for patients with NHL.
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PMID:Silencing of LIMD1 promotes proliferation and reverses cell adhesion-mediated drug resistance in non-Hodgkin's lymphoma. 3085 77