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PMID:9391078

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Citation

Melkonyan, HS, Chang, WC, Shapiro, JP, Mahadevappa, M, Fitzpatrick, PA, Kiefer, MC, Tomei, LD and Umansky, SR (1997) SARPs: a family of secreted apoptosis-related proteins. Proc. Natl. Acad. Sci. U.S.A. 94:13636-41

Abstract

Quiescent mouse embryonic C3H/10T1/2 cells are more resistant to different proapoptotic stimuli than are these cells in the exponential phase of growth. However, the exponentially growing 10T1/2 cells are resistant to inhibitors of RNA or protein synthesis, whereas quiescent cells die upon these treatments. Conditioned medium from quiescent 10T1/2 cells possesses anti-apoptotic activity, suggesting the presence of protein(s) that function as an inhibitor of the apoptotic program. Using differential display technique, we identified and cloned a cDNA designated sarp1 (secreted apoptosis-related protein) that is expressed in quiescent but not in exponentially growing 10T1/2 cells. Hybridization studies with sarp1 revealed two additional family members. Cloning and sequencing of sarp2 and sarp3 revealed 38% and 40% sequence identity to sarp1, respectively. Human breast adenocarcinoma MCF7 cells stably transfected with sarp1 or infected with SARP1-expressing adenovirus became more resistant, whereas cells transfected with sarp2 displayed increased sensitivity to different proapoptotic stimuli. Expression of sarp family members is tissue specific. sarp mRNAs encode secreted proteins that possess a cysteine-rich domain (CRD) homologous to the CRD of frizzled proteins but lack putative membrane-spanning segments. Expression of SARPs modifies the intracellular levels of beta-catenin, suggesting that SARPs interfere with the Wnt-frizzled proteins signaling pathway.

Links

PubMed PMC28358

Keywords

Amino Acid Sequence; Animals; Apoptosis/genetics; Apoptosis/physiology; Cell Division/genetics; Cell Line; Cloning, Molecular; Culture Media, Conditioned; Cytoskeletal Proteins/metabolism; Frizzled Receptors; Gene Expression; Humans; Interphase/genetics; Mice; Molecular Sequence Data; Multigene Family; Receptors, G-Protein-Coupled; Receptors, Neurotransmitter/genetics; Sequence Homology, Amino Acid; Signal Transduction; Tissue Distribution; Trans-Activators; Transfection; beta Catenin

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SFRP2

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SFRP5

involved_in

GO:0006915: apoptotic process

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SFRP1

involved_in

GO:1902043: positive regulation of extrinsic apoptotic signaling pathway via death domain receptors

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SFRP1

involved_in

GO:0071356: cellular response to tumor necrosis factor

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SFRP1

involved_in

GO:0090090: negative regulation of canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SFRP1

involved_in

GO:0043065: positive regulation of apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SFRP2

involved_in

GO:0030111: regulation of Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SFRP2

part_of

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SFRP2

involved_in

GO:1902042: negative regulation of extrinsic apoptotic signaling pathway via death domain receptors

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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