Aurora A site specific TACC3 phosphorylation regulates astral microtubule assembly by stabilizing γ-tubulin ring complex

Rajeev, Resmi; Singh, Puja; Asmita, Ananya; Anand, Ushma; Manna, Tapas

doi:10.1186/s12860-019-0242-z

Cited by 14 publications

(14 citation statements)

References 34 publications

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“…Additionally, modulating proteins are likewise vital for the regulation of centrosomal microtubule nucleation [ 12 ]. For example, TACC3 (transforming acidic coiled-coil-containing protein 3) has been found to stabilize γ-TuRC assembly from γ-TuSC [ 71 , 72 ]. The building components of γ-TuRC and its regulating proteins (activating, targeting, and anchoring) in the interphase centrosomes are summarized in Table 1 .…”

Section: γ-Tubulin and Microtubule Nucleation By γ-Tubulin Complexesmentioning

confidence: 99%

Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

Dráberová

2021

Cancers

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In cells, microtubules typically nucleate from microtubule organizing centers, such as centrosomes. γ-Tubulin, which forms multiprotein complexes, is essential for nucleation. The γ-tubulin ring complex (γ-TuRC) is an efficient microtubule nucleator that requires additional centrosomal proteins for its activation and targeting. Evidence suggests that there is a dysfunction of centrosomal microtubule nucleation in cancer cells. Despite decades of molecular analysis of γ-TuRC and its interacting factors, the mechanisms of microtubule nucleation in normal and cancer cells remains obscure. Here, we review recent work on the high-resolution structure of γ-TuRC, which brings new insight into the mechanism of microtubule nucleation. We discuss the effects of γ-TuRC protein dysregulation on cancer cell behavior and new compounds targeting γ-tubulin. Drugs inhibiting γ-TuRC functions could represent an alternative to microtubule targeting agents in cancer chemotherapy.

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Section: γ-Tubulin and Microtubule Nucleation By γ-Tubulin Complexesmentioning

confidence: 99%

Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

Dráberová

2021

Cancers

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“…However, inhibition of TACC3 expression has been detected as well [15]. It seems therefore that TACC3 plays different roles in different types of cancer [2][3][4][5][6][7][8][9][10][11][12][13][14][15].…”

Section: Discussionmentioning

confidence: 99%

“…It regulates the formation of microtubules throughout the cell cycle [1][2][3]. A great number of studies have shown that TACC3 is highly expressed in gastric cancer, cholangiocarcinoma, multiple myeloma, osteosarcoma, prostate cancer, glioblastoma and non-small cell lung cancer, and breast cancer [3][4][5][6][7][8][9][10][11][12]. However, inhibition of TACC3 expression has been detected in ovarian and thyroid cancers [13,14].…”

Section: Introductionmentioning

confidence: 99%

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The prognostic activity of transforming acidic coiled-coil 3 (TACC3) immunohistochemical expression in colon adenocarcinoma patients

Brzozowa-Zasada¹,

Wyrobiec²,

Piecuch³

et al. 2022

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Introduction: Colorectal cancer is most common in developed countries. Each year, more than one million people develop colon cancer, and nearly 70,000 people die from the disease. Although medicine has made great strides in the treatment of colorectal cancer, the prognosis of patients is still poor. It is difficult to find the main cause of colon cancer, so it is necessary to introduce new methods that will accurately diagnose the cause of this malignancy.Material and methods: Paraffin-embedded colon adenocarcinoma samples (n = 97) were assessed immunohistochemically for TACC3 protein. Connections between TACC3 immunoexpression and clinicopathological factors, including the 5-year overall survival (OS), were evaluated.Results: Immunohistochemical expression of TACC3 protein in colon adenocarcinoma samples and non-pathological samples of colon tissue was described as weak, moderate, or strong. As demonstrated, the level of the TACC3 immunohistochemical reactivity was not correlated with demographic factors including gender and age, and clinicopathological factors. The average survival time for all the patients was 36.8 months (95% CI: 33.134-40.536). A multivariate analysis demonstrated that the grade of tumour differentiation (HR = 2.740; 95% CI: 1.864-4.027, p < 0.001) and TACC3 immunoexpression in healthy tissues (HR = 1.700; 95% CI: 1.073-2.694) were independent risk factors for worse survival of patients.Conclusions: The high level of TACC3 immunoexpression in cancerous tissue was not associated with malignancy-related clinicopathological factors and 5-year overall survival of patients.

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“…These proteins likely affect microtubule nucleation more indirectly. As an example, TACC3 (transforming acidic coiled-coil containing protein 3) stabilizes γ-TuRC during its assembly from γ-TuSC (Singh et al, 2014;Rajeev et al, 2019). On the other hand the putative tumor suppressor cyclin-dependent kinase five regulatory subunitassociated protein 3 (CDK5RAP3; C53) (Wang et al, 2007), which exerts multiple functions in cell cycle regulation, DNA damage response, cell invasion, and ER homeostasis (Sheng et al, 2021), interacts with γ-TuRC and acts as a negative regulator of microtubule nucleation.…”

Section: γ-Turc Recruitment To Centrosomementioning

confidence: 99%

γ-Tubulin in microtubule nucleation and beyond

Sulimenko

Dráberová

2022

Front. Cell Dev. Biol.

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Microtubules composed of αβ-tubulin dimers are dynamic cytoskeletal polymers that play key roles in essential cellular processes such as cell division, organelle positioning, intracellular transport, and cell migration. γ-Tubulin is a highly conserved member of the tubulin family that is required for microtubule nucleation. γ-Tubulin, together with its associated proteins, forms the γ-tubulin ring complex (γ-TuRC), that templates microtubules. Here we review recent advances in the structure of γ-TuRC, its activation, and centrosomal recruitment. This provides new mechanistic insights into the molecular mechanism of microtubule nucleation. Accumulating data suggest that γ-tubulin also has other, less well understood functions. We discuss emerging evidence that γ-tubulin can form oligomers and filaments, has specific nuclear functions, and might be involved in centrosomal cross-talk between microtubules and microfilaments.

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Aurora A site specific TACC3 phosphorylation regulates astral microtubule assembly by stabilizing γ-tubulin ring complex

Cited by 14 publications

References 34 publications

Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

The prognostic activity of transforming acidic coiled-coil 3 (TACC3) immunohistochemical expression in colon adenocarcinoma patients

γ-Tubulin in microtubule nucleation and beyond

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