PMID- 10524633
OWN - NLM
STAT- MEDLINE
DCOM- 19991029
LR  - 20091119
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 401
IP  - 6753
DP  - 1999 Oct 7
TI  - 14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage.
PG  - 616-20
AB  - 14-3-3Sigma is a member of a family of proteins that regulate cellular activity
      by binding and sequestering phosphorylated proteins. It has been suggested that
      14-3-3sigma promotes pre-mitotic cell-cycle arrest following DNA damage, and that
      its expression can be controlled by the p53 tumour suppressor gene. Here we
      describe an improved approach to the generation of human somatic-cell knockouts, 
      which we have used to generate human colorectal cancer cells in which both
      14-3-3sigma alleles are inactivated. After DNA damage, these cells initially
      arrested in the G2 phase of the cell cycle, but, unlike cells containing
      14-3-3sigma, the 14-3-3sigma-/- cells were unable to maintain cell-cycle arrest. 
      The 14-3-3sigma-/- cells died ('mitotic catastrophe') as they entered mitosis.
      This process was associated with a failure of the 14-3-3sigma-deficient cells to 
      sequester the proteins (cyclin B1 and cdc2) that initiate mitosis and prevent
      them from entering the nucleus. These results may indicate a mechanism for
      maintaining the G2 checkpoint and preventing mitotic death.
FAU - Chan, T A
AU  - Chan TA
AD  - The Johns Hopkins Oncology Center, Program in Human Genetics, The Johns Hopkins
      University School of Medicine, Baltimore, Maryland 21231, USA.
FAU - Hermeking, H
AU  - Hermeking H
FAU - Lengauer, C
AU  - Lengauer C
FAU - Kinzler, K W
AU  - Kinzler KW
FAU - Vogelstein, B
AU  - Vogelstein B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (14-3-3 Proteins)
RN  - 0 (CCNB1 protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin B)
RN  - 0 (Cyclin B1)
RN  - 0 (Proteins)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 3.1.3.48 (CDC25C protein, human)
RN  - EC 3.1.3.48 (cdc25 Phosphatases)
SB  - IM
CIN - Nature. 1999 Oct 7;401(6753):535, 537. PMID: 10524615
MH  - 14-3-3 Proteins
MH  - Cell Cycle Proteins/physiology
MH  - Cloning, Molecular
MH  - Cyclin B/physiology
MH  - Cyclin B1
MH  - *DNA Damage
MH  - G2 Phase/physiology
MH  - Humans
MH  - Mitosis/*physiology
MH  - Proteins/genetics/*physiology
MH  - Tumor Cells, Cultured
MH  - *Tyrosine 3-Monooxygenase
MH  - cdc25 Phosphatases/physiology
EDAT- 1999/10/19 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/10/19 09:00
PHST- 1999/10/19 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/10/19 09:00 [entrez]
AID - 10.1038/44188 [doi]
PST - ppublish
SO  - Nature. 1999 Oct 7;401(6753):616-20. doi: 10.1038/44188.