The phosphorylation of p25/TPPP by LIM kinase 1 inhibits its ability to assemble microtubules

Acevedo, Karla; Li, Rong; Soo, Priscilla; Suryadinata, Randy; Šarčević, Boris; Valova, Valentina A.; Graham, Mark E.; Robinson, Phillip J.; Bernard, Ora

doi:10.1016/j.yexcr.2007.08.012

Cited by 62 publications

(90 citation statements)

References 26 publications

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“…The tendency of ␣-synuclein to form cytosolic aggregates is influenced by a number of other proteins, including synphilin-1 (22), protein interacting with NIMA 1 (PIN-1) (23), and TPPP/ p25␣ (hereafter referred to as p25␣) (24). The p25␣ protein binds to microtubules and by doing so lowers their plus-end growth rate and protects them from depolymerization (25)(26)(27). In addition, p25␣ potently stimulates aggregation of ␣-synuclein in vitro and localizes to Lewy bodies in vivo (24,28).…”

Section: Parkinson Disease (Pd)mentioning

confidence: 99%

Tubulin Polymerization-promoting Protein (TPPP/p25α) Promotes Unconventional Secretion of α-Synuclein through Exophagy by Impairing Autophagosome-Lysosome Fusion

Ejlerskov

Rasmussen

Nielsen

et al. 2013

Journal of Biological Chemistry

199

221

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Background:The mechanism of unconventional secretion of ␣-synuclein is unknown. Results: Autophagy of ␣-synuclein followed by exocytosis of autophagy intermediates (exophagy) are increased by expression of TPPP/p25␣. Conclusion: Exophagy of ␣-synuclein is increased by lysosomal dysfunction and/or altered trafficking of autophagosomes. Significance: Exophagy of ␣-synuclein might represent the first step in inter-neuronal spread of Lewy body disease.

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Section: Parkinson Disease (Pd)mentioning

confidence: 99%

Tubulin Polymerization-promoting Protein (TPPP/p25α) Promotes Unconventional Secretion of α-Synuclein through Exophagy by Impairing Autophagosome-Lysosome Fusion

Ejlerskov

Rasmussen

Nielsen

et al. 2013

Journal of Biological Chemistry

199

221

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“…2c). A particularly well-studied example is the action of tubulin polymerization-promoting protein-1 (TPPP1/p25) [43][44][45]. TPPP1 regulates MT acetylation and b-catenin expression by binding to HDAC6 and inhibiting its activity [44,45].…”

Section: Sam68mentioning

confidence: 99%

“…TPPP1 regulates MT acetylation and b-catenin expression by binding to HDAC6 and inhibiting its activity [44,45]. Overexpression of TPPP1 in cells promotes MT polymerization and an increase in MT acetylation, whereas introduction of TPPP1 RNAi reduces MT acetylation [43]. Phosphorylation of TPPP1 by Rho-associated coiled-coil kinase (ROCK) and cyclin-dependent kinase 1 (CDK1) impairs the interaction between TPPP1 and HDAC6, which, in turn, results in increased HDAC6 activity followed by a decrease in cell motility and an increase in cell proliferation, respectively [46,47].…”

Section: Sam68mentioning

confidence: 99%

Cellular defence or viral assist: the dilemma of HDAC6

Zheng

Jiang

et al. 2017

Journal of General Virology

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Histone deacetylase 6 (HDAC6) is a unique cytoplasmic deacetylase that regulates various important biological processes by preventing protein aggregation and deacetylating different non-histone substrates including tubulin, heat shock protein 90, cortactin, retinoic acid inducible gene I and b-catenin. Growing evidence has indicated a dual role for HDAC6 in viral infection and pathogenesis: HDAC6 may represent a host defence mechanism against viral infection by modulating microtubule acetylation, triggering antiviral immune response and stimulating protective autophagy, or it may be hijacked by the virus to enhance proinflammatory response. In this review, we will highlight current data illustrating the complexity and importance of HDAC6 in viral pathogenesis. We will summarize the structure and functional specificity of HDAC6, and its deacetylaseand ubiquitin-dependent activity in key cellular events in response to virus infection. We will also discuss how HDAC6 exerts its direct or indirect histone modification ability in viral lytic-latency switch.

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“…LIMKs are activated through phosphorylation by Rho-associated coiled-coil kinase (ROCK), p21-activated ki-nase 1 (PAK1) and PAK4, downstream effectors of the small GTPases Rho, Rac and Cdc42, respectively [3]- [5]. Interestingly, although it has been reported that LIMK1 and LIMK2 interact with Tubulin Polymerization Promoting Protein 1 (TPPP1) in vitro and in vivo [6]- [8], TPPP1 is not a LIMK substrate in cells [9].…”

Section: Introductionmentioning

confidence: 99%

LIMK1/TPPP1/HDAC6 Is a Dual Actin and Microtubule Regulatory Complex That Promotes Drug Resistance

Schofield¹,

Gamell²,

Bernard³

2014

ABB

Self Cite

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In this study, we identified a novel protein complex consisting of LIM-Kinase 1 (LIMK1), Histone deacetylase 6 (HDAC6) and Tubulin Polymerization Promoting Protein 1 (TPPP1). Under basal conditions, assembly of the LIMK1/TPPP1/HDAC6 complex results in both inhibition of HDAC6 activity and LIMK1 activation. This leads to increased microtubule (MT) acetylation, a MT stabilizing modification, and actin filament (F-actin) destabilization. In response to activation of the Rhokinase (ROCK) signaling pathway, downstream phosphorylation of LIMK1 and TPPP1 leads to the dissociation of the LIMK1/TPPP1/HDAC6 complex. In turn, HDAC6 and LIMK1 activities are increased, which results in MT destabilization and F-actin stabilization. Finally, we reveal that increasing tubulin acetylation reduces the efficacy of chemotherapeutic drugs, suggesting that strategies to reduce acetyl-tubulin levels may be a viable option in treating drug-resistant tumors.

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The phosphorylation of p25/TPPP by LIM kinase 1 inhibits its ability to assemble microtubules

Cited by 62 publications

References 26 publications

Tubulin Polymerization-promoting Protein (TPPP/p25α) Promotes Unconventional Secretion of α-Synuclein through Exophagy by Impairing Autophagosome-Lysosome Fusion

Tubulin Polymerization-promoting Protein (TPPP/p25α) Promotes Unconventional Secretion of α-Synuclein through Exophagy by Impairing Autophagosome-Lysosome Fusion

Cellular defence or viral assist: the dilemma of HDAC6

LIMK1/TPPP1/HDAC6 Is a Dual Actin and Microtubule Regulatory Complex That Promotes Drug Resistance

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