PMID- 10611237
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 20
IP  - 2
DP  - 2000 Jan
TI  - Alternatively spliced products CC3 and TC3 have opposing effects on apoptosis.
PG  - 583-93
AB  - The human gene CC3 is a metastasis suppressor for small cell lung carcinoma
      (SCLC) in vivo. The ability of CC3 to impair the apoptotic resistance of tumor
      cells is likely to contribute to metastasis suppression. We describe here an
      alternatively spliced RNA of CC3, designated TC3, that encodes an unstable
      protein with antiapoptotic activity. TC3 and CC3 proteins share amino-terminal
      sequences, but TC3 has a unique short hydrophobic carboxyl terminus.
      Overexpression of CC3 results in massive death of rodent fibroblasts, but TC3
      protects cells from CC3-induced death and from other death stimuli such as
      treatment with tumor necrosis factor or overexpression of Bax protein. The
      death-inducing activity of CC3 resides within its amino-terminal domain, which is
      conserved in TC3. The carboxyl terminus of TC3 is responsible for the
      antiapoptotic function of TC3; mutations in this domain abolish the ability of
      TC3 to protect cells from apoptosis. TC3 protein is short-lived due to its rapid 
      degradation by proteasome, and it forms complexes with a regulatory subunit of
      proteasome known as s5alpha. The signal for the rapid degradation of TC3 resides 
      within its carboxyl terminus, which is capable of conferring instability on a
      heterologous protein. The proapoptotic activity of CC3 in SCLC cells is induced
      by a wide variety of signals and involves disruption of the mitochondrial
      membrane potential (Deltapsim). The CC3 protein has sequence similarity to
      bacterial short-chain dehydrogenases/reductases and might represent a
      phylogenetically old effector of cell death similar to the recently identified
      apoptosis-inducing factor. CC3 and TC3 have opposing functions in apoptosis and
      represent a novel dual regulator of cell death.
FAU - Whitman, S
AU  - Whitman S
AD  - Cancer Research Institute, University of California San Francisco, San Francisco,
      California 94143, USA.
FAU - Wang, X
AU  - Wang X
FAU - Shalaby, R
AU  - Shalaby R
FAU - Shtivelman, E
AU  - Shtivelman E
LA  - eng
GR  - R01 CA71422/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (BAX protein, human)
RN  - 0 (Bax protein, rat)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 2.3.1.- (Acetyltransferases)
RN  - EC 2.3.1.48 (HTATIP2 protein, human)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - *Acetyltransferases
MH  - Alternative Splicing/*genetics
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Apoptosis/drug effects
MH  - Caspase Inhibitors
MH  - Caspases/metabolism
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Cloning, Molecular
MH  - Cysteine Endopeptidases/metabolism
MH  - DNA Fragmentation/drug effects
MH  - Half-Life
MH  - Humans
MH  - Intracellular Membranes/metabolism
MH  - Membrane Potentials
MH  - Mitochondria/physiology
MH  - Molecular Sequence Data
MH  - Multienzyme Complexes/metabolism
MH  - Mutation/genetics
MH  - Proteasome Endopeptidase Complex
MH  - Proto-Oncogene Proteins/genetics/physiology
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/physiology
MH  - RNA, Messenger/analysis/genetics
MH  - Rats
MH  - Transcription Factors/chemistry/*genetics/*metabolism
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - bcl-2-Associated X Protein
PMC - PMC85138
EDAT- 1999/12/28 00:00
MHDA- 1999/12/28 00:01
CRDT- 1999/12/28 00:00
PHST- 1999/12/28 00:00 [pubmed]
PHST- 1999/12/28 00:01 [medline]
PHST- 1999/12/28 00:00 [entrez]
AID - 10.1128/MCB.20.2.583-593.2000 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2000 Jan;20(2):583-93. doi: 10.1128/MCB.20.2.583-593.2000.