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Literature summary for 3.4.23.B24 extracted from

  • Hsu, F.F.; Chou, Y.T.; Chiang, M.T.; Li, F.A.; Yeh, C.T.; Lee, W.H.; Chau, L.Y.
    Signal peptide peptidase promotes tumor progression via facilitating FKBP8 degradation (2019), Oncogene, 38, 1688-1701 .
    View publication on PubMed
Search for more literature for 3.4.23.B24

Cloned(Commentary)

Cloned (Comment) Organism
gene sppA, recombinant expression of HA-tagged enzyme SppA in HeLa cells, coexpression with FKBP8 Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information lung (H-1299) and breast (MCF-7 and MDA-MB-231) cancer cell lines with stable SPP knockdown mediated by two different specific shRNAs targeting SPP are established. Stable depletion of SPP expression in lung and breast cancer cell lines significantly reduces cell growth and migration/invasion abilities Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
endoplasmic reticulum membrane SPP colocalizes with FKBP8 Homo sapiens 5789
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Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
FKBP8 + H2O Homo sapiens
-
 ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
breast
-
 Homo sapiens
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breast cancer cell high expression level Homo sapiens
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colon
-
 Homo sapiens
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lung
-
 Homo sapiens
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lung cancer cell high expression level Homo sapiens
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MCF-7 cell
-
 Homo sapiens
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MDA-MB-231 cell
-
 Homo sapiens
-
NCI-H1299 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
FKBP8 + H2O
-
 Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
SPP
-
 Homo sapiens

Expression

Organism Comment Expression
Homo sapiens SPP expression is highly induced in human lung and breast cancers and correlated with disease outcome up

General Information

General Information Comment Organism
malfunction stable depletion of SPP expression in lung and breast cancer cell lines significantly reduces cell growth and migration/invasion abilities. The level of FKBP8, an endogenous inhibitor of mTOR, is significantly increased following SPP depletion, and the levels of phosphorylation in mTOR and its downstream effectors, S6K and 4E-BP1, are significantly lower in SPP-depleted cells. The reduced mTOR signaling and decreases of growth and migration/invasion abilities induced by SPP depletion in cancer cells can be reversed by FKBP8 downregulation. Downregulation of SPP suppresses cell growth, migration, and invasion, cell phenotypes, overview Homo sapiens
physiological function signal peptide peptidase (SPP) is an endoplasmic reticulum (ER)-resident aspartyl protease mediating intramembrane cleavage of type II transmembrane proteins, role of SPP in ER-associated protein degradation. SPP expression is highly induced in human lung and breast cancers and correlated with disease outcome. SPP interacts and colocalizes with FKBP8 in the endoplasmic reticulum. SPP-mediated proteolysis facilitates FKBP8 protein degradation in the cytosol. SPP promotes tumor progression, at least in part, via facilitating the degradation of FKBP8 to enhance mTOR signaling Homo sapiens