| 1. |
- Alvarado Kristensson, Maria, et al.
(författare)
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The Biology of the Nuclear Envelope and Its Implications in Cancer Biology
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 20:10
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Forskningsöversikt (refereegranskat)abstract
- The formation of the nuclear envelope and the subsequent compartmentalization of the genome is a defining feature of eukaryotes. Traditionally, the nuclear envelope was purely viewed as a physical barrier to preserve genetic material in eukaryotic cells. However, in the last few decades, it has been revealed to be a critical cellular component in controlling gene expression and has been implicated in several human diseases. In cancer, the relevance of the cell nucleus was first reported in the mid-1800s when an altered nuclear morphology was observed in tumor cells. This review aims to give a current and comprehensive view of the role of the nuclear envelope on cancer first by recapitulating the changes of the nuclear envelope during cell division, second, by reviewing the role of the nuclear envelope in cell cycle regulation, signaling, and the regulation of the genome, and finally, by addressing the nuclear envelope link to cell migration and metastasis and its use in cancer prognosis.
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| 2. |
- Ehlén, Åsa, et al.
(författare)
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Tumors with non-functional RB1 are killed by reduced gamma-tubulin levels.
- 2012
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 287:21, s. 17241-17247
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Tidskriftsartikel (refereegranskat)abstract
- In various tumors inactivation of growth control is achieved by interfering with the RB1 signaling pathway. Here, we describe that RB1 and γ tubulin proteins moderate each other's expression by binding to their respective gene promoters. Simultaneous reduction of RB1 and γ tubulin protein levels result in an E2F1-dependent upregulation of apoptotic genes such as caspase 3. We report that in various tumors types, there is an inverse correlation between the expression levels of γ tubulin and RB1 and that in tumor cell lines with a non-functioning RB1, reduction of γ tubulin protein levels leads to induction of apoptosis. Thus, the RB1/γ tubulin signal network can be considered as a new target for cancer treatment.
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| 3. |
- Lindström, Lisa, et al.
(författare)
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The GTPase domain of gamma-tubulin is required for normal mitochondrial function and spatial organization
- 2018
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1:https://doi.org/10.1038/s42003-018-0037-3
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Tidskriftsartikel (refereegranskat)abstract
- In the cell, γ-tubulin establishes a cellular network of threads named the γ-string meshwork. However, the functions of this meshwork remain to be determined. We investigated the traits of the meshwork and show that γ-strings have the ability to connect the cytoplasm and the mitochondrial DNA together. We also show that γ-tubulin has a role in the maintenance of the mitochondrial network and functions as reduced levels of γ-tubulin or impairment of its GTPase domain disrupts the mitochondrial network and alters both their respiratory capacity and the expression of mitochondrial-related genes. By contrast, reduced mitochondrial number or increased protein levels of γ-tubulin DNA-binding domain enhanced the association of γ-tubulin with mitochondria. Our results demonstrate that γ-tubulin is an important mitochondrial structural component that maintains the mitochondrial network, providing mitochondria with a cellular infrastructure. We propose that γ-tubulin provides a cytoskeletal element that gives form to the mitochondrial network.
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| 4. |
- Rosselló, Catalina Ana, et al.
(författare)
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γ-Tubulin⁻γ-Tubulin Interactions as the Basis for the Formation of a Meshwork
- 2018
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 19:10
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Forskningsöversikt (refereegranskat)abstract
- In cytoplasm, protein γ-tubulin joins with various γ-tubulin complex proteins (GCPs) to form a heterotetramer γ-tubulin small complex (γ-TuSC) that can grow into a ring-shaped structure called the γ-tubulin ring complex (γ-TuRC). Both γ-TuSC and γ-TuRC are required for microtubule nucleation. Recent knowledge on γ-tubulin with regard to its cellular functions beyond participation in its creation of microtubules suggests that this protein forms a cellular meshwork. The present review summarizes the recognized functions of γ-tubulin and aims to unite the current views on this protein.
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| 5. |
- Rossello Castillo, Catalina Ana, et al.
(författare)
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Gamma-tubulin coordinates nuclear envelope assembly around chromatin
- 2016
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 2:9
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Tidskriftsartikel (refereegranskat)abstract
- The cytosolic role of γ-tubulin as a microtubule organizer has been studied thoroughly, but its nuclear function is poorly understood. Here, we show that γ-tubulin is located throughout the chromatin of demembranated Xenopus laevis sperm and, as the nucleus is formed, γ-tubulin recruits lamin B3 and nuclear membranes. Immunodepletion of γ-tubulin impairs X. laevis assembly of both the lamina and the nuclear membrane. During nuclear formation in mammalian cell lines, γ-tubulin establishes a cellular protein boundary around chromatin that coordinates nuclear assembly of the daughter nuclei. Furthermore, expression of a γ-tubulin mutant that lacks the DNA-binding domain forms chromatin-empty nuclear like structures and demonstrate that a constant interplay between the chromatin-associated and the cytosolic pools of γ-tubulin is required and, when the balance between pools is impaired, aberrant nuclei are formed. We therefore propose that the nuclear protein meshwork formed by γ-tubulin around chromatin coordinates nuclear formation in eukaryotic cells.
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