scholarly journals Chromosome region maintenance 1 expression and its association with clinical pathological features in primary carcinoma of the liver

2016 ◽  
Vol 12 (1) ◽  
pp. 59-68 ◽  
Author(s):  
QIAO-LING XIE ◽  
YUE LIU ◽  
YING ZHU
Keyword(s):  
Chromosome Region ◽  
Primary Carcinoma ◽  
Pathological Features ◽  
Chromosome Region Maintenance

Preclinical activity of SL-801, a reversible inhibitor of Exportin-1 (XPO1)/Chromosome Region Maintenance-1 (CRM1) in solid and hematologic cancers.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e13543-e13543
Author(s):  
Janice Chen ◽  
Christopher L. Brooks ◽  
Peter McDonald ◽  
Jonathan D. Schwartz ◽  
Keiichi Sakakibara ◽  
...  
Keyword(s):  
Chromosome Region ◽  
Reversible Inhibitor ◽  
Chromosome Region Maintenance

scholarly journals A Carboxyl Leucine-Rich Region of Parathyroid Hormone-Related Protein Is Critical for Nuclear Export

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 990-998 ◽  
Author(s):  
Jared C. Pache ◽  
Douglas W. Burton ◽  
Leonard J. Deftos ◽  
Randolph H. Hastings
Keyword(s):  
Amino Acid ◽  
Nuclear Export ◽  
Chromosome Region ◽  
Nuclear Export Signal ◽  
Wild Type ◽  
Leptomycin B ◽  
Intact Cells ◽  
Parathyroid Hormone Related Protein ◽  
Truncation Mutant ◽  
Chromosome Region Maintenance

PTHrP is an oncofetal protein with distinct proliferative and antiapoptotic roles that are affected by nucleocytoplasmic shuttling. The protein’s nuclear export is sensitive to leptomycin B, consistent with a chromosome region maintenance protein 1-dependent pathway. We determined that the 109–139 region of PTHrP was involved in its nuclear export by demonstrating that a C-terminal truncation mutant, residues 1–108, exports at a reduced rate, compared with the wild-type 139 amino acid isoform. We searched for potential nuclear export sequences within the 109–139 region, which is leucine rich. Comparisons with established nuclear export sequences identified a putative consensus signal at residues 126–136. Deletion of this region resulted in nuclear export characteristics that closely matched those of the C-terminal truncation mutant. Confocal microscopic analyses of transfected 293, COS-1, and HeLa cells showed that steady-state nuclear levels of the truncated and deletion mutants were significantly greater than levels of wild-type PTHrP and were unaffected by leptomycin B, unlike the wild-type protein. In addition, both mutants demonstrated greatly reduced nuclear export with assays using nuclear preparations and intact cells. Based on these results, we conclude that the 126–136 amino acid sequence closely approximates the structure of a chromosome region maintenance protein 1-dependent leucine-rich nuclear export signal and is critical for nuclear export of PTHrP.

scholarly journals Molecular Docking Studies of α-Pyrone Derivatives Isolated from Alternaria phragmospora as CRM1 Inhibitors

2020 ◽  
Author(s):  
Ahmed Metwaly ◽  
Ibrahim Eissa ◽  
Ahmad Mostafa
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Chromosome Region ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Chemically Modified ◽  
Structure Activity ◽  
Modes Of Interaction ◽  
Chromosome Region Maintenance

Some α-Pyrone derivatives isolated from Alternaria phragmospora fungus showed promising anti leukemic activities, while others were inactive. CRM1/XPO1 (chromosome region maintenance 1 protein, also called exportin1 or PO1 in humans) has been chosen as a target for antileukemic molecular docking study for those compounds to understand their modes of interaction and structure activity relationships. The results showed that two (2 and 4), out of six, natural α-Pyrone derivatives exhibited well-established interactions with the amino acids of the receptor, which was in agreement with the experimental anti-leukemic results of these compounds. Moreover, twenty hypothetical chemically modified α-Pyrone derivatives (7-27) have been designed. Compounds 7, 8, 22 and 24 showed more efficient docking properties than the previously considered natural compounds.

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