Àá½Ã¸¸ ±â´Ù·Á ÁÖ¼¼¿ä. ·ÎµùÁßÀÔ´Ï´Ù.
KMID : 0578320220450060413
Molecules and Cells
2022 Volume.45 No. 6 p.413 ~ p.424
SMAD4 Controls Cancer Cell Metabolism by Regulating Methylmalonic Aciduria Cobalamin Deficiency (cbl) B Type
Song Kyoung

Lee Hun-Seok
Jia Lina
Chelakkot Chaithanya
Rajasekaran Nirmal
Shin Young-Kee
Abstract
Suppressor of mothers against decapentaplegic homolog (SMAD) 4 is a pluripotent signaling mediator that regulates myriad cellular functions, including cell growth, cell division, angiogenesis, apoptosis, cell invasion, and metastasis, through transforming growth factor ¥â (TGF-¥â)-dependent and -independent pathways. SMAD4 is a critical modulator in signal transduction and functions primarily as a transcription factor or cofactor. Apart from being a DNA-binding factor, the additional SMAD4 mechanisms in tumor suppression remain elusive. We previously identified methyl malonyl aciduria cobalamin deficiency B type (MMAB) as a critical SMAD4 binding protein using a proto array analysis. This study confirmed the interaction between SMAD4 and MMAB using bimolecular fluorescence complementation (BiFC) assay, proximity ligation assay (PLA), and conventional immunoprecipitation. We found that transient SMAD4 overexpression down-regulates MMAB expression via a proteasome-dependent pathway. SMAD4-MMAB interaction was independent of TGF-¥â signaling. Finally, we determined the effect of MMAB downregulation on cancer cells. siRNA-mediated knockdown of MMAB affected cancer cell metabolism in HeLa cells by decreasing ATP production and glucose consumption as well as inducing apoptosis. These findings suggest that SMAD4 controls cancer cell metabolism by regulating MMAB.
KEYWORD
methyl malonyl aciduria cobalamin deficiency B type, mitochondrial energy production, proteasomal pathway, suppressor of mothers against decapentaplegic homolog 4
FullTexts / Linksout information
Listed journal information
SCI(E) MEDLINE ÇмúÁøÈïÀç´Ü(KCI)