PMID- 10508612
OWN - NLM
STAT- MEDLINE
DCOM- 20000214
LR  - 20190728
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 9
IP  - 18
DP  - 1999 Sep 23
TI  - Evidence for a function of death-receptor-related, death-domain-containing
      proteins in anoikis.
PG  - 1047-9
AB  - Normal epithelial cells undergo apoptosis if integrinmediated matrix contacts are
      lost, in a process termed 'anoikis'. Anoikis prevents shed epithelial cells from 
      colonizing elsewhere, and is thus essential for maintaining appropriate tissue
      organisation. Aberrant oncogenes or tumor suppressor genes can cause resistance
      to anoikis, thereby contributing substantially to malignancy. Apoptosis is
      mediated by a well-ordered signaling cascade, which involves activation of
      intracellular proteases known as caspases. However, the mechanism by which the
      caspase cascade is initiated following cell-matrix detachment is unknown. We have
      hypothesized that death receptor activation might be involved in anoikis. To test
      this hypothesis, we developed a transient assay for anoikis and used it to assay 
      the effects of proteins that block the function of domains found within death
      receptors known as death domains. In this assay, silencer of death domains (SODD)
      and dominant-negative FAS-associated death domain protein (FADD) efficiently
      inhibited anoikis in Madin-Darby canine kidney (MDCK) cells. The protective
      activity of SODD required its BAG domain, which interacts with the heat shock
      proteins hsp70 and hsc70, and inhibits the chaperone activity of the latter. Both
      caspase 8, which physically associates with death receptors, and cleavage of the 
      caspase-8 substrate BID, were activated by cell-matrix detachment. These findings
      indicate a role for death receptors or proteins with related death domains in
      triggering anoikis.
FAU - Frisch, S M
AU  - Frisch SM
AD  - The Burnham Institute 10901 North Torrey Pines Road, La Jolla, California 92037, 
      USA. sfrisch@burnham-inst.org
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Arabidopsis Proteins)
RN  - 0 (BH3 Interacting Domain Death Agonist Protein)
RN  - 0 (Carrier Proteins)
RN  - 0 (HSC70 Heat-Shock Proteins)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Peptide Fragments)
RN  - EC 1.14.19.- (Fatty Acid Desaturases)
RN  - EC 1.14.99.- (Fad7 protein, Arabidopsis)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - *Arabidopsis Proteins
MH  - BH3 Interacting Domain Death Agonist Protein
MH  - Carrier Proteins/antagonists & inhibitors/chemistry/metabolism/*physiology
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/*physiology
MH  - Cell Adhesion/*physiology
MH  - Cell Line
MH  - Dogs
MH  - Enzyme Activation
MH  - Epithelial Cells/cytology
MH  - Extracellular Matrix/physiology
MH  - Fatty Acid Desaturases/chemistry/*physiology
MH  - HSC70 Heat-Shock Proteins
MH  - HSP70 Heat-Shock Proteins/metabolism
MH  - Kidney
MH  - Models, Biological
MH  - Peptide Fragments/metabolism
MH  - Protein Structure, Tertiary
MH  - Signal Transduction
EDAT- 1999/10/06 09:00
MHDA- 2000/02/19 09:00
CRDT- 1999/10/06 09:00
PHST- 1999/10/06 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 1999/10/06 09:00 [entrez]
AID - S0960-9822(99)80455-2 [pii]
AID - 10.1016/s0960-9822(99)80455-2 [doi]
PST - ppublish
SO  - Curr Biol. 1999 Sep 23;9(18):1047-9. doi: 10.1016/s0960-9822(99)80455-2.