PMID- 10411904
OWN - NLM
STAT- MEDLINE
DCOM- 19990823
LR  - 20191210
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 15
DP  - 1999 Jul 20
TI  - TID1, a human homolog of the Drosophila tumor suppressor l(2)tid, encodes two
      mitochondrial modulators of apoptosis with opposing functions.
PG  - 8499-504
AB  - Mitochondria have emerged as central regulators of apoptosis. Here, we show that 
      TID1, a human homolog of the Drosophila tumor suppressor lethal (2) tumorous
      imaginal discs, l(2)tid, encodes two mitochondrial matrix proteins, designated
      hTid-1(L) and hTid-1(S). These splice variants are both highly conserved members 
      of the DnaJ family of proteins, which regulate the activity of and confer
      substrate specificity to Hsp70 proteins. Both hTid-1(L) and hTid-1(S)
      coimmunoprecipitate with mitochondrial Hsp70. Expression of hTid-1(L) or
      hTid-1(S) have no apparent capacity to induce apoptosis but have opposing effects
      on apoptosis induced by exogenous stimuli. Expression of hTid-1(L) increases
      apoptosis induced by both the DNA-damaging agent mitomycin c and tumor necrosis
      factor alpha. This activity is J domain-dependent, because a J domain mutant of
      hTid-1(L) can dominantly suppress apoptosis. In sharp contrast, expression of
      hTid-1(S) suppresses apoptosis, whereas expression of a J domain mutant of
      hTid-1(S) increases apoptosis. Hence, we propose that TID1 gene products act to
      positively and negatively modulate apoptotic signal transduction or effector
      structures within the mitochondrial matrix.
FAU - Syken, J
AU  - Syken J
AD  - Department of Pathology and Harvard Center for Cancer Biology, Harvard Medical
      School, Boston, MA 02115, USA.
FAU - De-Medina, T
AU  - De-Medina T
FAU - Munger, K
AU  - Munger K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (CG5504 protein, Drosophila)
RN  - 0 (Cytochrome c Group)
RN  - 0 (DNAJA3 protein, human)
RN  - 0 (Drosophila Proteins)
RN  - 0 (HSP40 Heat-Shock Proteins)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 50SG953SK6 (Mitomycin)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apoptosis/*genetics
MH  - Caspases/metabolism
MH  - Cloning, Molecular
MH  - Cytochrome c Group/metabolism
MH  - Drosophila/*genetics
MH  - *Drosophila Proteins
MH  - Genes, Tumor Suppressor/*genetics
MH  - HSP40 Heat-Shock Proteins
MH  - HSP70 Heat-Shock Proteins/metabolism
MH  - Heat-Shock Proteins/chemistry/*genetics
MH  - Humans
MH  - Microscopy, Fluorescence
MH  - Mitochondria/*chemistry
MH  - Mitochondrial Proteins
MH  - Mitomycin/pharmacology
MH  - Molecular Sequence Data
MH  - Signal Transduction
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/pharmacology
PMC - PMC17545
EDAT- 1999/07/21 00:00
MHDA- 1999/07/21 00:01
CRDT- 1999/07/21 00:00
PHST- 1999/07/21 00:00 [pubmed]
PHST- 1999/07/21 00:01 [medline]
PHST- 1999/07/21 00:00 [entrez]
AID - 10.1073/pnas.96.15.8499 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8499-504. doi:
      10.1073/pnas.96.15.8499.