3'-(p-azidobenzamido)taxol photolabels the N-terminal 31 amino acids of beta-tubulin.

Rao, Srinivasa P. S.; Krauss, Nancy E.; Heerding, Julia M.; Swindell, Charles S.; Ringel, Israel; Orr, George A.; Horwitz, Susan Band

doi:10.1016/s0021-9258(17)41836-9

Cited by 238 publications

(70 citation statements)

References 29 publications

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“…These observations support the hypothesis that LPS and taxol share a common target in a signaling pathway controlled by the Lps gene (12). Although LPS and taxol may activate such a target directly from the cell surface, both enter cells rapidly (17,18) and bind specifically to [3-tubulin in a cell-free system (19)(20)(21). Thus, whether they are activated directly or indirectly, the common target of LPS and taxol may be MAP.…”

supporting

confidence: 73%

Association of mitogen-activated protein kinases with microtubules in mouse macrophages.

Ding

Chen

Fuortes

et al. 1996

The Journal of Experimental Medicine

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SummaryTaxol, a microtubule-binding diterpene, mimics many effects of lipopolysaccharide (LPS) on mouse macrophages. The LPS-mimetic effects of taxol appear to be under the same genetic control as responses to LPS itself. Thus we have postulated a role for microtubule-associated proteins (MAP) in the response of macrophages to LPS. Stimulation of macrophages by LPS quickly induces the activation of mitogen-activated protein kinases (MAPK). MAPK are generally considered cytosolic enzymes. Herein we report that much of the LPS-activatable pool of MAPK in primary mouse peritoneal macrophages is microtubule associated. By immunofluorescence, MAPK were localized to colchicine-and nocodazole-disruptible filaments. From both mouse brain and RAW 264.7 macrophages, MAPK could be coisolated with polymerized tubulin. Fractionation of primary macrophages into cytosol-, microfilament-, microtubule-, and intermediate filament-rich extracts revealed that "~10% of MAPK but none ofMAPK kinase (MEK1 and MEK2) was microtubule bound. Exposure of macrophages to LPS did not change the proportion of MAPK bound to microtubules, but preferentially activated the microtubule-associated pool. These findings confirm the prediction that LPS activates a kinase bound to microtubules. Together with LPS-mimetic actions of taxol and the shared genetic control of responses to LPS and taxol, these results support the hypothesis that a major LPS-signaling pathway in mouse macrophages may involve activation of one or more microtubuleassociated kinases.

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supporting

confidence: 73%

Association of mitogen-activated protein kinases with microtubules in mouse macrophages.

Ding

Chen

Fuortes

et al. 1996

The Journal of Experimental Medicine

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“…The mechanism of stabilization is not known, but there have been two recent reports on crosslinking photoactive taxol derivatives to tubulin. One indicates that taxol interacts with an amino-terminal region (31 amino acids in length) of 3-tubulin [13], and the other indicates a 2.5-fold higher labeling of P-tubulin than a-tubulin [14]. It has also been reported that microtubules assembled in the presence of taxol tend to have 12, rather than 13, protofilaments [15,16].…”

Section: Introductionmentioning

confidence: 99%

How does taxol stabilize microtubules?

1995

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“…Our data confirmed additivity in those cells lines that undergo paclitaxel-induced ERK activation, and antagonism in cells with low ERK activity, suggesting that in tumors with high ERK activity, there may be an application for this strategy in therapy.Paclitaxel (Taxol) is a widely used cancer chemotherapeutic drug that exhibits clinical activity in a range of human malignancies (Arbuck et al, 1993) and is being extensively evaluated in ongoing trials as a single agent (Malingre et al, 2000) and in combination therapy (Piccart et al, 2000). The binding site for paclitaxel on β-tubulin has been assigned from photoaffinity labeling experiments (Rao et al, 1994(Rao et al, , 1995(Rao et al, , 1999 and from the electron crystallography model in which the αand β-tubulin dimer is fitted to a 3.7-Å density map (Nogales et al, 1998). In addition to its ability to bind to microtubules, paclitaxel also has been shown to interact with bcl-2 (Rodi et al, 1999) and to phosphorylate both bcl-2 and…”

mentioning

confidence: 99%

Selective Potentiation of Paclitaxel (Taxol)-Induced Cell Death by Mitogen-Activated Protein Kinase Kinase Inhibition in Human Cancer Cell Lines

2001

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Activation of the mitogen-activated protein kinase (MAPK) pathway in HeLa and Chinese hamster ovary cells after treatment with paclitaxel (Taxol) and other microtubule interacting agents has been investigated. Using a trans-reporting system, the phosphorylation of the nuclear transcription factors Elk-1 and c-jun was measured. Concentration- and time-dependent activation of the Elk-1 pathway, mediated primarily by the extracellular signal-regulated kinase (ERK) component of the MAPK family, was observed. Inactive drug analogs and other cytotoxic compounds that do not target microtubules failed to induce similar levels of activation, thereby indicating that an interaction between these drugs and the microtubule is essential for the activation of MAPKs. Evaluation of the endogenous levels of MAPK expression revealed cell-dependent expression of the ERK, c-jun N-terminal kinase, and p38 pathways. In the case of HeLa cells, time-dependent activation of ERK coincided with increased poly(ADP-ribose) polymerase (PARP) cleavage, phosphatidylserine externalization, and increased accumulation of cells in G2/M. In both cell lines, inhibition of ERK activity potentiated paclitaxel-induced PARP cleavage and phosphatidylserine externalization, suggesting that ERK activity coincided with, but did not mediate, the cytotoxic effects of paclitaxel. We evaluated the nature of the interaction between paclitaxel and the MAPK kinase inhibitor U0126 in three cell lines, on the basis of a potential chemotherapeutic advantage of paclitaxel plus ERK inhibition. Our data confirmed additivity in those cells lines that undergo paclitaxel-induced ERK activation, and antagonism in cells with low ERK activity, suggesting that in tumors with high ERK activity, there may be an application for this strategy in therapy.

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3'-(p-azidobenzamido)taxol photolabels the N-terminal 31 amino acids of beta-tubulin.

Cited by 238 publications

References 29 publications

Association of mitogen-activated protein kinases with microtubules in mouse macrophages.

Association of mitogen-activated protein kinases with microtubules in mouse macrophages.

How does taxol stabilize microtubules?

Selective Potentiation of Paclitaxel (Taxol)-Induced Cell Death by Mitogen-Activated Protein Kinase Kinase Inhibition in Human Cancer Cell Lines

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