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Literature summary for 3.6.5.2 extracted from

  • Shen, D.W.; Pouliot, L.M.; Gillet, J.P.; Ma, W.; Johnson, A.C.; Hall, M.D.; Gottesman, M.M.
    The transcription factor GCF2 is an upstream repressor of the small GTPAse RhoA, regulating membrane protein trafficking, sensitivity to doxorubicin, and resistance to cisplatin (2012), Mol. Pharm., 9, 1822-1833.
    View publication on PubMedView publication on EuropePMC

Protein Variants

Protein Variants Comment Organism
additional information gene silencing by transfection of anti-RhoA siRNA Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism

Organism UniProt Comment Textmining
Homo sapiens P61586
-
-

Source Tissue

Source Tissue Comment Organism Textmining
KB-3-1 cell
-
Homo sapiens
-
KB-CP.5 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GTP + H2O
-
Homo sapiens GDP + phosphate
-
?

Synonyms

Synonyms Comment Organism
RhoA
-
Homo sapiens
small GTPase
-
Homo sapiens

General Information

General Information Comment Organism
malfunction increased expression of GCF2 is found in human chemotherapeutic agent cisplatin-resistant cells, and overexpression in GCF2-transfected cells results in loss of RhoA expression and disruption of the actin-filamin network. The membrane transporter MRP1 is internalized from the cell surface into the cytoplasm, rendering cells sensitive to doxorubicin by more than 10fold due to increased accumulation of doxorubicin in the cells. The GCF2 transfectants also show reduced accumulation of cisplatin and increased resistance. siRNA targeted to GCF2 suppresses the expression of GCF2 in cisplatin-resistant cells, reactivates RhoA expression, and restores the fine structure of actin microfilaments. MRP1 is also relocated to the cell surface. siRNA targeted to RhoA increased resistance 3fold in KB-3-1 and KB-CP.5 cells. Phenotypes, overview. Silencing RhoA increases resistance against cisplatin Homo sapiens
metabolism a complex regulatory pathway downstream from GCF2 involves the small GTPase RhoA, actin/filamin dynamics, and membrane protein trafficking, overview Homo sapiens
physiological function the transcription factor GCF2 is an upstream repressor of the small GTPAse RhoA, regulating membrane protein trafficking, sensitivity to doxorubicin, and resistance to cisplatin. GC-binding factor 2 (GCF2)/leucine-rich repeat (in FLII) interacting protein 1 (LRRFIP1) directly interacts with Dishevelled protein to regulate RhoA activity Homo sapiens