ABCMdb

ABCB1 p.Asp26Glu

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Publications

PMID: 16505100 [PubMed] Hari M et al: "Paclitaxel-resistant cells have a mutation in the paclitaxel-binding region of beta-tubulin (Asp26Glu) and less stable microtubules."

No. Sentence Comment

123 Sequencing revealed that class I h-tubulin of KB-15-PTX/099 cells encodes for a point mutation at residue Asp26 Glu (GAT to GAA) compared with the wild-type sequence (see Supplementary Fig. S1).3 This mutation is in the NH2 terminus of h-tubulin and is part of the binding pocket of paclitaxel (ref. 34; see Discussion). Login to comment
125 Amino acid sequencing confirmed that the Asp26 Glu mutation was expressed in the h-tubulin protein isolated from KB-15-PTX/099 cells. Login to comment
154 These cells (a) are resistant to paclitaxel and cross-resistant to other tubulin polymerizing agents, yet are collaterally sensitive to microtubule depolymerizing agents; (b) are partially growth-dependent on paclitaxel or other tubulin polymerizing drugs; (c) contain a mutation in h-tubulin protein that substitutes glutamate for aspartate at position 26; and (d) have less stable microtubules compared with parental cells. Login to comment
174 The mutation in h-tubulin Asp26 Glu is unique because it seems to be in the contact site for paclitaxel but is also associated with a change in microtubule stability. Login to comment
175 In support of the important role of Asp26 in paclitaxel binding and tubulin function, a h-tubulin mutation converting Asp26 to glutamate was also recently reported in paclitaxel-resistant Chinese hamster ovary cells (37). Login to comment
176 The exogenous expression of Asp26 Glu h-tubulin in a wild-type background conferred resistance to paclitaxel and sensitivity to colcemid and vinblastine. Login to comment
183 Reappearance of wild-type tubulin could also be explained by the selection of revertants because cells bearing the Asp26 Glu mutation depend on paclitaxel for growth and may not survive extended passage without the drug. Login to comment
184 Asp26 Mutation The mutation of Asp26 to glutamate in h-tubulin detected in KB-15-PTX/099 cells is likely to reside in a contact site for paclitaxel based on biochemical and structural studies. Login to comment
214 To examine the effect of the Asp26 Glu mutation, we adopted a strategy that initially examined the different rotamers of the glutamate residue in the mutant in the energy-optimized models. Login to comment
224 Analysis of nonbonded interactions in the separate h-tubulin models of paclitaxel, docetaxel, and MAC-321 implies that relative binding affinities to the Asp26 Glu mutant in the KB-15-PTX/099 cell line are paclitaxel < docetaxel V MAC-321. Login to comment
227 In general, tighter binding drugs should increase rather than decrease cell kill, assuming that the only change in assay and cell conditions is the Asp26 Glu mutation. Login to comment
245 The Asp26 Glu point mutation is at the drug binding site and is associated with a change in the stability of microtubules. Login to comment

PMID: 25499884 [PubMed] Busschots S et al: "Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells."

No. Sentence Comment

411 [63] M. Hari, F. Loganzo, T. Annable, X. Tan, S. Musto, D.B. Morilla, J.H. Nettles, J.P. Snyder, L.M. Greenberger, Paclitaxel-resistant cells have a mutation in the paclitaxel-binding region of Beta-tubulin (Asp26Glu) and less stable microtubules, Mol. Cancer Ther. 5 (2) (2006) 270-278. Login to comment