Dephosphorylation in nuclear reassembly after mitosis

Abstract

In most animal cell types, the interphase nucleus is largely disassembled during mitotic entry. The nuclear envelope breaks down and chromosomes are compacted into separated masses. Chromatin organization is also mostly lost and kinetochores assemble on centromeres. Mitotic protein kinases play several roles in inducing these transformations by phosphorylating multiple effector proteins. In many of these events, the mechanistic consequences of phosphorylation have been characterized. In comparison, how the nucleus reassembles at the end of mitosis is less well understood in mechanistic terms. In recent years, much progress has been made in deciphering how dephosphorylation of several effector proteins promotes nuclear envelope reassembly, chromosome decondensation, kinetochore disassembly and interphase chromatin organization. The precise roles of protein phosphatases in this process, in particular of the PP1 and PP2A groups, are emerging. Moreover, how these enzymes are temporally and spatially regulated to ensure that nuclear reassembly progresses in a coordinated manner has been partly uncovered. This review provides a global view of nuclear reassembly with a focus on the roles of dephosphorylation events. It also identifies important open questions and proposes hypotheses.

Protein Phosphatase 4 Is Required for Centrobin Function in DNA Damage Repair

“…Understanding the molecular etiology of cancer plays an indispensable role in shaping the future of cancer diagnosis and personalized therapy for patients. The Ser/Thr protein phosphatase 4, PP4, has been extensively studied and found to play a critical role in several cellular processes, including cell cycle regulation [ 15 , 24 , 30 , 31 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ] and DNA repair [ 16 , 17 , 19 , 61 , 62 , 63 , 64 ]. The impact of PP4 on cancer development has been investigated, revealing that alterations in PP4 expression, subcellular localization, or activity can contribute to tumorigenesis.…”

Sculpting nuclear envelope identity from the endoplasmic reticulum during the cell cycle

“…For nuclear lamins, their mitotic phosphorylation causes depolymerization, leading to the dispersal of A-type lamins across the cytoplasm, while B-type lamins remain associated with mitotic ER membranes [ 22 , 23 ]. For INM proteins, such as lamin B receptor (LBR), lamina-associated polypeptide 2 (LAP2), emerin, MAN1 domain (LEM domain) proteins, and SUN1, their phosphorylation disrupts their interactions with chromatin, the nuclear lamina, and other INM proteins [ 24 , 25 ]. This disruption allows the INM proteins to separate from the nuclear periphery.…”

“…Phosphorylation of the barrier-to-autointegration factor (BAF), which in its unphosphorylated form connects LEM domain proteins to chromatin in interphase, also promotes the disruption of the links between LEM domain proteins and chromatin during mitosis [ 26 ]. A list of mitotic kinases/phosphatases and their substrates involved in NE breakdown/assembly is summarized in another review [ 24 ].…”

“…What mediates the attachment of ER membranes to the chromosome surface during mitotic exit at the molecular level? After anaphase onset, the phosphorylation events that induce NEBD at prophase are reversed by the inactivation of mitotic kinases such as CDK1 and the reactivation of phosphatases such as protein phosphatase 1 (PP1) and 2A (PP2A) [ 15 , 24 ]. This makes lamins, INM proteins, and nucleoporins competent for rebinding to chromatin and to each other.…”

Close Ties between the Nuclear Envelope and Mammalian Telomeres: Give Me Shelter

“…The mechanisms involved in telomere anchoring is not yet elucidated but may require the SUN1 and RAP1 proteins [ 112 ], but it could also rely on different proteins such as lamins and other shelterin proteins than RAP1, since interactions between lamin A and TRF2 [ 113 ] and between lamin B1 and both TRF1 and TRF2, have been reported [ 112 , 114 , 115 ]. During mitosis, the NE breaks down and the NPC disassembles, followed by lamina depolymerization, with the release of lamin A into the nucleoplasm in prophase [ 116 , 117 ], while lamin B1 remains associated in fragmented polymerized fibers with membrane protein aggregates [ 118 , 119 ]. Furthermore, lamin B1 begins to concentrate around chromosomes at the anaphase–telophase transition and assembles into fibers at an early step of the NE reassembly [ 120 ], while lamin A is incorporated in lamina much later, in G1.…”