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Mitochondrial targeting of growth suppressor protein DLC2 through the START domain
Authors:Ng David Chi-Heng  Chan Shing-Fai  Kok Kin Hang  Yam Judy Wai Ping  Ching Yick-Pang  Ng Irene Oi-Lin  Jin Dong-Yan
Affiliation:Department of Biochemistry, Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Abstract: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.
Keywords:DLC2, deleted in liver cancer 2   GAP, GTPase activating protein   HCC, hepatocellular carcinoma   PBS, phosphate buffered saline   SAM, sterile α-motif   SRE, serum response element   StAR, steroidogenic acute regulatory protein   START, steroidogenic acute regulatory protein-related lipid transfer   TRITC, tetramethylrhodamine isothiocyanate
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