PMID- 10200466
OWN - NLM
STAT- MEDLINE
DCOM- 19990507
LR  - 20121115
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 5
IP  - 3
DP  - 1998 Mar
TI  - The adenomatous polyposis coli protein and retinoblastoma protein are cleaved
      early in apoptosis and are potential substrates for caspases.
PG  - 206-13
AB  - Apoptosis in human monocytic THP.1 tumour cells, induced by diverse stimuli, was 
      accompanied by proteolytic cleavage of the adenomatous polyposis coli gene
      product (APC) and by sequential cleavage of the retinoblastoma susceptibility
      gene product (Rb). Cleavage of poly(ADP-ribose) polymerase (PARP), APC and the
      initial cleavage of Rb at the carboxy terminal region all occurred at a similar
      time, early in the apoptotic process. Subsequently, Rb underwent a secondary
      cleavage to 43 kDa and 30 kDa protein fragments. Two caspase inhibitors,
      benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone (Z-VAD.FMK) and
      acetyl-Tyr-Val-Ala-Asp chloromethyl ketone (YVAD.CMK), had markedly different
      effects on the induction of apoptosis. Z-VAD.FMK inhibited the primary and
      secondary cleavage of Rb, cleavage of APC and PARP, and apoptosis assessed by
      flow cytometry. In marked contrast, YVAD.CMK inhibited cleavage of APC and the
      secondary cleavage of Rb to the 43 kDa and 30 kDa protein fragments but did not
      inhibit the primary carboxy terminal cleavage of Rb, PARP proteolysis or
      apoptosis assessed by flow cytometry. These results suggest that different
      caspases are responsible for the cleavage of different substrates at different
      stages during the apoptotic process and that a caspase may either cleave APC
      directly or may be involved in the pathway leading to APC proteolysis. This is
      the first report suggesting that a cytoplasmic tumour suppressor gene (APC) may
      be cleaved by a caspase during apoptosis.
FAU - Browne, S J
AU  - Browne SJ
AD  - CRC Colorectal Tumour Biology Research Group, Department of Pathology and
      Microbiology, University of Bristol, Bristol, UK.
FAU - MacFarlane, M
AU  - MacFarlane M
FAU - Cohen, G M
AU  - Cohen GM
FAU - Paraskeva, C
AU  - Paraskeva C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (Adenomatous Polyposis Coli Protein)
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Adenomatous Polyposis Coli Protein
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Apoptosis/drug effects/*physiology
MH  - Caspase Inhibitors
MH  - Caspases/*metabolism
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Cytoskeletal Proteins/*metabolism
MH  - Humans
MH  - Neoplasm Proteins/*metabolism
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Retinoblastoma Protein/*metabolism
MH  - Substrate Specificity
MH  - Tumor Cells, Cultured
EDAT- 1999/04/14 00:00
MHDA- 1999/04/14 00:01
CRDT- 1999/04/14 00:00
PHST- 1999/04/14 00:00 [pubmed]
PHST- 1999/04/14 00:01 [medline]
PHST- 1999/04/14 00:00 [entrez]
AID - 10.1038/sj.cdd.4400331 [doi]
PST - ppublish
SO  - Cell Death Differ. 1998 Mar;5(3):206-13. doi: 10.1038/sj.cdd.4400331.