Tpr regulates the total number of nuclear pore complexes per cell nucleus

McCloskey, Asako; Ibarra, Arkaitz; Hetzer, Martin W.

doi:10.1101/gad.315523.118

Cited by 47 publications

(36 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, both yeast aging datasets and the rat liver proteomes show that the levels of the Mlp1/Tpr proteins (and the other basket Nups human Nup50 and yeast Nup2) decrease relative to the other Nups. As the absence of Tpr is reported to increase NPC numbers , this could indicate that more NPCs are assembled in aging. This is not in line with the decline in NPC number reported in rat liver , but it is in line with the overall increase in Nup levels at the NE in yeast .…”

Section: Potential Causes For Age‐related Changes Of Npcs: Assembly Amentioning

confidence: 96%

“…Extracellular signal‐regulated kinase phosphorylates Tpr at the NPC, and while associated with the NPC, it also phosphorylates Nup153. Phosphorylation of Nup153 then prevents Nup153's association with the outer ring complex and blocks further NPC assembly . Cancer cells often have more NPCs , and there is evidence suggesting that NPC numbers also change in aging .…”

Section: Potential Causes For Age‐related Changes Of Npcs: Assembly Amentioning

confidence: 99%

See 1 more Smart Citation

Poor old pores—The challenge of making and maintaining nuclear pore complexes in aging

2020

View full text Add to dashboard Cite

The nuclear pore complex (NPC) is the sole gateway to the nuclear interior, and its function is essential to all eukaryotic life. Controlling the functionality of NPCs is a tremendous challenge for cells. Firstly, NPCs are large structures, and their complex assembly does occasionally go awry. Secondly, once assembled, some components of the NPC persist for an extremely long time and, as a result, are susceptible to accumulate damage. Lastly, a significant proportion of the NPC is composed of intrinsically disordered proteins that are prone to aggregation. In this review, we summarize how the quality of NPCs is guarded in young cells and discuss the current knowledge on the fate of NPCs during normal aging in different tissues and organisms. We discuss the extent to which current data supports a hypothesis that NPCs are poorly maintained during aging of nondividing cells, while in dividing cells the main challenge is related to the assembly of new NPCs. Our survey of current knowledge points toward NPC quality control as an important node in aging of both dividing and nondividing cells. Here, the loss of protein homeostasis during aging is central and the NPC appears to both be impacted by, and to drive, this process.

show abstract

Section: Potential Causes For Age‐related Changes Of Npcs: Assembly Amentioning

confidence: 96%

Section: Potential Causes For Age‐related Changes Of Npcs: Assembly Amentioning

confidence: 99%

Poor old pores—The challenge of making and maintaining nuclear pore complexes in aging

2020

View full text Add to dashboard Cite

show abstract

“…NPC numbers also change as a function of normal physiological processes such as differentiation [ 137 , 138 ]. The nuclear basket protein TPR negatively regulates NPC numbers in human cells [ 139 ]. This activity is controlled via the ERK signaling pathway [ 139 ].…”

Section: Changes In the Npc Associated With Mrna Export And Cancermentioning

confidence: 99%

“…The nuclear basket protein TPR negatively regulates NPC numbers in human cells [ 139 ]. This activity is controlled via the ERK signaling pathway [ 139 ]. This provides a means to link proliferative signaling and NPC number and thus could be related to cancer.…”

Section: Changes In the Npc Associated With Mrna Export And Cancermentioning

confidence: 99%

The Nuclear Pore Complex and mRNA Export in Cancer

Borden

2020

Cancers

View full text Add to dashboard Cite

Export of mRNAs from the nucleus to the cytoplasm is a key regulatory step in the expression of proteins. mRNAs are transported through the nuclear pore complex (NPC). Export of mRNAs responds to a variety of cellular stimuli and stresses. Revelations of the specific effects elicited by NPC components and associated co-factors provides a molecular basis for the export of selected RNAs, independent of bulk mRNA export. Aberrant RNA export has been observed in primary human cancer specimens. These cargo RNAs encode factors involved in nearly all facets of malignancy. Indeed, the NPC components involved in RNA export as well as the RNA export machinery can be found to be dysregulated, mutated, or impacted by chromosomal translocations in cancer. The basic mechanisms associated with RNA export with relation to export machinery and relevant NPC components are described. Therapeutic strategies targeting this machinery in clinical trials is also discussed. These findings firmly position RNA export as a targetable feature of cancer along with transcription and translation.

show abstract

“…Additionally, interesting to resolve is the question of whether there is a sequence-specific selection of eccDNAs, which might have a peculiar affinity to SAGA-mediated NPC attachment. As basket Tpr, the human homolog of yeast Mlp1/2, was shown to regulate the absolute number of NPCs within the nuclear envelope [139], it might constitute one of the putative SAGA targets in mammals. In support of this, in humans, the TREX-2 complex, which interacts with SAGA, has recently been shown to stably localize to the pore basket through interactions with basket Nup153 and Tpr [140].…”

Section: Role In Neurodegenerative Disordersmentioning

confidence: 99%

Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration

Ain

Schmeer

Wengerodt

et al. 2020

IJMS

View full text Add to dashboard Cite

Still unresolved is the question of how a lifetime accumulation of somatic gene copy number alterations impact organ functionality and aging and age-related pathologies. Such an issue appears particularly relevant in the broadly post-mitotic central nervous system (CNS), where non-replicative neurons are restricted in DNA-repair choices and are prone to accumulate DNA damage, as they remain unreplaced over a lifetime. Both DNA injuries and consecutive DNA-repair strategies are processes that can evoke extrachromosomal circular DNA species, apparently from either part of the genome. Due to their capacity to amplify gene copies and related transcripts, the individual cellular load of extrachromosomal circular DNAs will contribute to a dynamic pool of additional coding and regulatory chromatin elements. Analogous to tumor tissues, where the mosaicism of circular DNAs plays a well-characterized role in oncogene plasticity and drug resistance, we suggest involvement of the “circulome” also in the CNS. Accordingly, we summarize current knowledge on the molecular biogenesis, homeostasis and gene regulatory impacts of circular extrachromosomal DNA and propose, in light of recent discoveries, a critical role in CNS aging and neurodegeneration. Future studies will elucidate the influence of individual extrachromosomal DNA species according to their sequence complexity and regional distribution or cell-type-specific abundance.

show abstract

Tpr regulates the total number of nuclear pore complexes per cell nucleus

Cited by 47 publications

References 48 publications

Poor old pores—The challenge of making and maintaining nuclear pore complexes in aging

Poor old pores—The challenge of making and maintaining nuclear pore complexes in aging

The Nuclear Pore Complex and mRNA Export in Cancer

Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration

Contact Info

Product

Resources

About