AKAP12 induces apoptotic cell death in human fibrosarcoma cells by regulating CDKI-cyclin D1 and caspase-3 activity.
AKAP12 (A-Kinase anchoring protein 12) is a protein kinase C substrate and a potential tumor suppressor. AKAP12 is down-regulated by several oncogenes and strongly suppressed in various cancers including prostate, ovarian and breast cancers. AKAP12 acts as a regulator of mitogenesis by anchoring key signal proteins such as PKA, PKC, and cyclins. In this study, AKAP12 was found to suppress tumor cell viability by inducing apoptosis via caspase-3 in HT1080 cells. This AKAP12-induced apoptosis was associated with a decreased expression of Bcl-2 and increased expression of Bax. Moreover, AKAP12-transfectant strongly induced the expression of Cip1/p21 and Kip1/p27, but resulted in a decrease in cyclin D1 involved in G(1) progression. Accordingly, these results suggest that AKAP12 may play an important role in tumor growth suppression by inducing apoptosis with the regulation of multiple molecules in the cell cycle progression.
Yoon
Dae-Kwan
DK
NeuroVascular Coordination Research Center, Division of Pharmaceutical Biosciences, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Jeong
Chul-Ho
CH
Jun
Hyoung Oh
HO
Chun
Kwang-Hoon
KH
Cha
Jong-Ho
JH
Seo
Ji Hae
JH
Lee
Hae Young
HY
Choi
Yoon Kyung
YK
Ahn
Bum-Ju
BJ
Lee
Seung-Ki
SK
Kim
Kyu-Won
KW
D054758:A Kinase Anchor Proteins; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D019938:Cyclin D1 / Q000378:metabolism*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D053938:DNA Fragmentation; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D016193:G1 Phase / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; C494826:BAX protein, human; C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047908:Intracellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D053148:Caspase 3