Nucleoporins redistribute inside the nucleus after cell cycle arrest induced by histone deacetylases inhibition

Abstract

(2017) Nucleoporins redistribute inside the nucleus after cell cycle arrest induced by histone deacetylases inhibition, Nucleus, 8:5, 515-533, DOI: 10.1080/19491034.2017 To link to this article: https://doi.org/10. 1080/19491034.2017 ABSTRACTNucleoporins are the main components of the nuclear-pore complex (NPC) and were initially considered as mere structural elements embedded in the nuclear envelope, being responsible for nucleocytoplasmic transport. Nevertheless, several recent scientific reports have revealed that some nucleoporins participate in nuclear processes such as transcription, replication, DNA repair and chromosome segregation. Thus, the interaction of NPCs with chromatin could modulate the distribution of chromosome territories relying on the epigenetic state of DNA. In particular, the nuclear basket proteins Tpr and Nup153, and the FG-nucleoporin Nup98 seem to play key roles in all these novel functions. In this work, histone deacetylase inhibitors (HDACi) were used to induce a hyperacetylated state of chromatin and the behavior of the mentioned nucleoporins was studied. Our results show that, after HDACi treatment, Tpr, Nup153 and Nup98 are translocated from the nuclear pore toward the interior of the cell nucleus, accumulating as intranuclear nucleoporin clusters. These transitory structures are highly dynamic, and are mainly present in the population of cells arrested at the G0/G1 phase of the cell cycle. Our results indicate that the redistribution of these nucleoporins from the nuclear envelope to the nuclear interior may be implicated in the early events of cell cycle initialization, particularly during the G1 phase transition.

Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells

“…While rarely found in WT mESCs, such Tpr-positive/Nup153-negative foci were detected in a large fraction of Nup133 −/− mESCs (Fig 3C). The absence of Nup153 distinguishes these foci from NPCs present on long NE invaginations, a common feature of nuclei in undifferentiated mESCs (Luo et al, 2009), and from intranuclear Nup clusters recently described in G0/G1 arrested cells (Perez-Garrastachu et al, 2017). However, this observation is reminiscent of the relocation of Tpr into intranuclear aggregates upon depletion of Nup153 in HeLa cells (Hase and Cordes, 2003) and suggests that a fraction of the Tpr protein not assembled into NPCs localizes to the nucleoplasm of Nup133 −/− mESCs.…”

Parental genome unification is highly error-prone in mammalian embryos

“…Notably, the pronuclear volume was decreased suggesting that NPC function was partially impaired ( Figure S6 J). The nuclear basket of the NPC, which protrudes into the nucleoplasm, could mediate chromatin binding ( Arlucea et al., 1998 ; Ibarra and Hetzer, 2015 ; Pérez-Garrastachu et al., 2017 ). However, depletion of the nuclear basket proteins TPR and Nup153 by Trim-Away did not affect chromosome clustering, recruitment into the outer nuclear region, or pronuclear size ( Figures S6 K and S6L).…”

The Nuclear Pore Complex: A Target for NS3 Protease of Dengue and Zika Viruses

“…In contrast, at 24 hpi with ZIKV, a significant reduction in the amount of TPR, Nup153, and Nup98, but not in the amount of Nup62, was observed ( Figure 2 C). These results strongly suggest that DENV and ZIKV infection induced the cleavage/degradation of some Nups involved in the nuclear-cytoplasmic transport, in that Nup153 and Nup98 were altered in both DENV and ZIKV infection [ 43 ].…”