Mitochondrial targeting of growth suppressor protein DLC2 through the START domain.
Deleted in liver cancer 2 (DLC2) is a candidate tumor suppressor frequently found to be deleted in hepatocellular carcinoma. In this study, we determined the subcellular localization of DLC2. Co-localization and biochemical fractionation studies revealed that DLC2 localized to mitochondria. In addition, the DLC2-containing cytoplasmic speckles were in proximity to lipid droplets. A DLC2 mutant containing the steroidogenic acute regulatory protein-related lipid transfer (START) domain only showed a localization pattern identical to that of DLC2. Taken together, we have provided the first evidence for mitochondrial localization of DLC2 through the START domain. These findings might have implications in liver physiology and carcinogenesis.
Ng
David Chi-Heng
DC
Department of Biochemistry, Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Chan
Shing-Fai
SF
Kok
Kin Hang
KH
Yam
Judy Wai Ping
JW
Ching
Yick-Pang
YP
Ng
Irene Oi-Lin
IO
Jin
Dong-Yan
DY
D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000098682:Steroidogenic Acute Regulatory Protein
D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; C473607:STARD13 protein, human; D025521:Tumor Suppressor Proteins; D000098682:Steroidogenic Acute Regulatory Protein