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PMID:22770216

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Citation

Asencio, C, Davidson, IF, Santarella-Mellwig, R, Ly-Hartig, TB, Mall, M, Wallenfang, MR, Mattaj, IW and Gorjánácz, M (2012) Coordination of kinase and phosphatase activities by Lem4 enables nuclear envelope reassembly during mitosis. Cell 150:122-35

Abstract

Mitosis in metazoa requires nuclear envelope (NE) disassembly and reassembly. NE disassembly is driven by multiple phosphorylation events. Mitotic phosphorylation of the protein BAF reduces its affinity for chromatin and the LEM family of inner nuclear membrane proteins; loss of this BAF-mediated chromatin-NE link contributes to NE disassembly. BAF must reassociate with chromatin and LEM proteins at mitotic exit to reform the NE; however, how its dephosphorylation is regulated is unknown. Here, we show that the C. elegans protein LEM-4L and its human ortholog Lem4 (also called ANKLE2) are both required for BAF dephosphorylation. They act in part by inhibiting BAF's mitotic kinase, VRK-1, in vivo and in vitro. In addition, Lem4/LEM-4L interacts with PP2A and is required for it to dephosphorylate BAF during mitotic exit. By coordinating VRK-1- and PP2A-mediated signaling on BAF, Lem4/LEM-4L controls postmitotic NE formation in a function conserved from worms to humans.

Links

PubMed Online version:10.1016/j.cell.2012.04.043

Keywords

Animals; Caenorhabditis elegans/cytology; Caenorhabditis elegans/enzymology; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Carrier Proteins/metabolism; DNA-Binding Proteins/metabolism; HeLa Cells; Humans; Membrane Proteins/chemistry; Membrane Proteins/metabolism; Mitosis; Mutation; Nuclear Envelope/metabolism; Nuclear Proteins/chemistry; Nuclear Proteins/metabolism; Protein Phosphatase 2/metabolism; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:PP2A

involved_in

GO:0007084: mitotic nuclear membrane reassembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:PP2A

involved_in

GO:0007084: mitotic nuclear membrane reassembly

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00021945

P

Seeded From UniProt

complete

CAEEL:ANKL2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q03565

F

Seeded From UniProt

complete

CAEEL:ANKL2

involved_in

GO:0007084: mitotic nuclear membrane reassembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:ANKL2

located_in

GO:0005635: nuclear envelope

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:ANKL2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q19848

F

Seeded From UniProt

complete

CAEEL:ANKL2

involved_in

GO:0007084: mitotic nuclear membrane reassembly

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002363

P

Seeded From UniProt

complete

HUMAN:BAF

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q86XL3

F

Seeded From UniProt

complete

CAEEL:BAF1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:H2KZB2

F

Seeded From UniProt

complete

CAEEL:BAF1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q19848

F

Seeded From UniProt

complete

CAEEL:VRK1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:H2KZB2

F

Seeded From UniProt

complete

CAEEL:VRK1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q03565

F

Seeded From UniProt

complete

CAEEL:VRK1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q86XL3

F

Seeded From UniProt

complete

CAEEL:VRK1

enables

GO:0004672: protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(WB:WBGene00000235)

Seeded From UniProt

complete

HUMAN:ANKL2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75531

F

Seeded From UniProt

complete

HUMAN:ANKL2

enables

GO:0019888: protein phosphatase regulator activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ANKL2

located_in

GO:0030176: integral component of endoplasmic reticulum membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ANKL2

involved_in

GO:0007084: mitotic nuclear membrane reassembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ANKL2

involved_in

GO:0050790: regulation of catalytic activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ANKL2

enables

GO:0051721: protein phosphatase 2A binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ANKL2

involved_in

GO:0042326: negative regulation of phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ANKL2

involved_in

GO:0035307: positive regulation of protein dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ANKL2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q19848

F

Seeded From UniProt

complete

CAEEL:ANKL2

involved_in

GO:0035307: positive regulation of protein dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:ANKL2

involved_in

GO:0042326: negative regulation of phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:ANKL2

part_of

GO:0005635: nuclear envelope

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:ANKL2

enables

GO:0051721: protein phosphatase 2A binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:ANKL2

involved_in

GO:0007084: mitotic nuclear envelope reassembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:ANKL2

involved_in

GO:0007084: mitotic nuclear envelope reassembly

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00002363

P

Seeded From UniProt

complete


See also

References

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