PMID- 10395539
OWN - NLM
STAT- MEDLINE
DCOM- 19990917
LR  - 20190728
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 9
IP  - 13
DP  - 1999 Jul 1
TI  - Translocation of cyclin B1 to the nucleus at prophase requires a
      phosphorylation-dependent nuclear import signal.
PG  - 680-9
AB  - BACKGROUND: At M phase, cyclin B1 is phosphorylated in the cytoplasmic retention 
      sequence (CRS), which is required for nuclear export. During interphase, cyclin
      B1 shuttles between the nucleus and the cytoplasm because constitutive nuclear
      import is counteracted by rapid nuclear export. In M phase, cyclin B moves
      rapidly into the nucleus coincident with its phosphorylation, an overall movement
      that might be caused simply by a decrease in its nuclear export. However, the
      questions of whether CRS phosphorylation is required for cyclin B1 translocation 
      in mitosis and whether a reduction in nuclear export is sufficient to explain its
      rapid relocalisation have not been addressed. RESULTS: We have used two forms of 
      green fluorescent protein to analyse simultaneously the translocation of
      wild-type cyclin B1 and a phosphorylation mutant of cyclin B1 in mitosis, and
      correlated this with an in vitro nuclear import assay. We show that cyclin B1
      rapidly translocates into the nucleus approximately 10 minutes before breakdown
      of the nuclear envelope, and that this movement requires the CRS phosphorylation 
      sites. A cyclin B1 mutant that cannot be phosphorylated enters the nucleus after 
      the wild-type protein. Phosphorylation of the CRS creates a nuclear import signal
      that enhances cyclin B1 import in vitro and in vivo, in a manner distinct from
      the previously described import of cyclin B1 mediated by importin beta.
      CONCLUSIONS: We show that phosphorylation of human cyclin B1 is required for its 
      rapid translocation to the nucleus towards the end of prophase. Phosphorylation
      enhances cyclin B1 nuclear import by creating a nuclear import signal. The
      phosphorylation of the CRS is therefore a critical step in the control of
      mitosis.
FAU - Hagting, A
AU  - Hagting A
AD  - Wellcome/CRC Institute, Department of Zoology, Tennis Court Road, Cambridge, CB2 
      1QR, UK.
FAU - Jackman, M
AU  - Jackman M
FAU - Simpson, K
AU  - Simpson K
FAU - Pines, J
AU  - Pines J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (CCNB1 protein, human)
RN  - 0 (Cyclin B)
RN  - 0 (Cyclin B1)
RN  - 0 (Membrane Proteins)
RN  - 0 (cell-surface retention-binding protein 1)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cell Cycle/physiology
MH  - Cell Nucleus/*metabolism
MH  - Cyclin B/genetics/*metabolism
MH  - Cyclin B1
MH  - HeLa Cells
MH  - Humans
MH  - Membrane Proteins/chemistry/*metabolism
MH  - Microscopy, Fluorescence
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Phosphorylation
MH  - Prophase/*physiology
MH  - Sequence Alignment
MH  - Time Factors
EDAT- 1999/07/08 00:00
MHDA- 1999/07/08 00:01
CRDT- 1999/07/08 00:00
PHST- 1999/07/08 00:00 [pubmed]
PHST- 1999/07/08 00:01 [medline]
PHST- 1999/07/08 00:00 [entrez]
AID - S0960-9822(99)80308-X [pii]
AID - 10.1016/s0960-9822(99)80308-x [doi]
PST - ppublish
SO  - Curr Biol. 1999 Jul 1;9(13):680-9. doi: 10.1016/s0960-9822(99)80308-x.