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Literature summary for 1.1.1.27 extracted from

  • Brisson, L.; Banski, P.; Sboarina, M.; Dethier, C.; Danhier, P.; Fontenille, M.J.; Van Hee, V.F.; Vazeille, T.; Tardy, M.; Falces, J.; Bouzin, C.; Porporato, P.E.; Frederick, R.; Michiels, C.; Copetti, T.; Sonveaux, P.
    Lactate dehydrogenase B controls lysosome activity and autophagy in cancer (2016), Cancer Cell, 30, 418-431.
    View publication on PubMed

Application

Application Comment Organism
medicine LDHB is a therapeutic target in cancer Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information silencing of LDHB with a small interfering RNA (siRNA) (siLDHB-2) decreasing cell number in all the cancer cell lines investigated Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm
-
Homo sapiens 5737
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(S)-lactate + NAD+ Homo sapiens
-
pyruvate + NADH + H+
-
r

Organism

Organism UniProt Comment Textmining
Homo sapiens P07195
-
-

Source Tissue

Source Tissue Comment Organism Textmining
cervix adenocarcinoma cell
-
Homo sapiens
-
colon carcinoma cell
-
Homo sapiens
-
glioblastoma cell
-
Homo sapiens
-
HCT-116 cell
-
Homo sapiens
-
HeLa cell
-
Homo sapiens
-
MCF-7 cell
-
Homo sapiens
-
ovarian carcinoma cell
-
Homo sapiens
-
SiHa cell
-
Homo sapiens
-
SKOV-3 cell
-
Homo sapiens
-
T-98G cell
-
Homo sapiens
-
U-373 cell
-
Homo sapiens
-
WiDr cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(S)-lactate + NAD+
-
Homo sapiens pyruvate + NADH + H+
-
r

Synonyms

Synonyms Comment Organism
lactate dehydrogenase B
-
Homo sapiens
LDHB
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NAD+
-
Homo sapiens
NADH
-
Homo sapiens

General Information

General Information Comment Organism
malfunction silencing LDHB selectively inhibits the proliferation of both oxidative and glycolytic cancer cells over normal cells, targeting LDHB selectively blocks autophagy in oxidative and glycolytic cancer cells, but siLDHB does not affect the subcellular distribution pattern of lysosomes and their distance to the cell nucleus. siLDHB induces lysosomal inhibition in oxidative cancer cells. Overexpression of LDHB decreases the number of acidic vesicles per cell. LDHB overexpression increases mature autolysosome formation and intracellular proteolysis in SiHa and in HeLa cells. LDHB reaction substrate lactate and product pyruvate do not metabolically restore autophagy and intracellular proteolysis in LDHB-depleted SiHa cells, but LDHB-depleted cells switch to a glycolytic metabolism Homo sapiens
physiological function lactate dehydrogenase B (LDHB), catalyzing the conversion of lactate and NAD+ to pyruvate, NADH and H+, controls lysosomal acidification, vesicle maturation, and intracellular proteolysis. LDHB activity is necessary for basal autophagy and cancer cell proliferation not only in oxidative cancer cells but also in glycolytic cancer cells. Lactate supports lysosomal acidification and autophagy in cancer. Lactate oxidation by LDHB yields protons that fuel lysosomal V-ATPase. LDHB is critical for lysosomal activity and autophagy in cancer cells. LDHB controls early tumor progression and the number of cancer cells, and negatively affects patient survival. Lactate promotes LDHB-dependent autophagy in oxidative cancer cells Homo sapiens