PMID- 11722574
OWN - NLM
STAT- MEDLINE
DCOM- 20011231
LR  - 20190620
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 268
IP  - 22
DP  - 2001 Nov
TI  - SCCA2 inhibits TNF-mediated apoptosis in transfected HeLa cells. The reactive 
      centre loop sequence is essential for this function and TNF-induced cathepsin G 
      is a candidate target.
PG  - 5868-75
AB  - The squamous cell carcinoma antigens, SCCA1 and SCCA2, are members of the serine 
      protease inhibitors (serpin) superfamily and are transcribed by two tandomly 
      arrayed genes. A number of serpins are known to inhibit apoptosis in mammalian 
      cells. In this study we demonstrate the ability of SCCA2 to inhibit tumor 
      necrosis factor-alpha (TNF alpha)-induced apoptosis. HeLa cells stably 
      transfected with SCCA2 cDNA had increased percentage cell survival and reduced 
      DNA fragmentation. We investigated if the reactive centre loop (RCL) was 
      necessary to allow SCCA2 to inhibit TNF alpha-mediated apoptosis. The RCL amino 
      acids (E353Q, L354G, S355A), flanking the predicted cleavage site, were mutated 
      and the resulting SCCA2 lost both the ability to inhibit cathepsin G and to 
      protect stably transfected cells from TNF alpha-induced apoptosis. The presence 
      of SCCA2 caused a decrease in the activation of caspase-3 upon induction with TNF 
      alpha but no direct inhibition of caspases by SCCA2 has been found. Expression of 
      cathepsin G was found to be induced in HeLa cells following treatment with TNF 
      alpha. This protease has recently been shown to have a role in apoptosis through 
      cleavage of substrates, so maybe the relevant target for SCCA2 in this system.
FAU - McGettrick, A F
AU  - McGettrick AF
AD  - Department of Biochemistry and Conway Institute of Biomolecular and Biomedical 
      Research, University College Dublin, Belfield, Dublin 4, Ireland.
FAU - Barnes, R C
AU  - Barnes RC
FAU - Worrall, D M
AU  - Worrall DM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Serpins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (squamous cell carcinoma-related antigen)
RN  - EC 3.4.- (Cathepsins)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.20 (CTSG protein, human)
RN  - EC 3.4.21.20 (Cathepsin G)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Antigens, Neoplasm/genetics/*physiology
MH  - Apoptosis/*physiology
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cathepsin G
MH  - Cathepsins/biosynthesis
MH  - Enzyme Induction
MH  - Escherichia coli/genetics
MH  - HeLa Cells
MH  - Humans
MH  - Mutagenesis, Site-Directed
MH  - Recombinant Proteins/metabolism
MH  - Serine Endopeptidases
MH  - *Serpins
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*physiology
EDAT- 2001/11/28 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/11/28 10:00
PHST- 2001/11/28 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/11/28 10:00 [entrez]
AID - 2535 [pii]
AID - 10.1046/j.0014-2956.2001.02535.x [doi]
PST - ppublish
SO  - Eur J Biochem. 2001 Nov;268(22):5868-75. doi: 10.1046/j.0014-2956.2001.02535.x.