Mitochondrial ribosomal protein L41 suppresses cell growth in association with p53 and p27Kip1.
The p53 protein arrests the cell cycle at the G1 phase when stabilized by the interaction between ribosomal proteins and HDM2 under growth-inhibitory conditions. Meanwhile, p53, when translocated to the mitochondria in response to cell death signals, induces apoptosis via transcription-independent mechanisms. In this report, we demonstrate that the mitochondrial ribosomal protein L41 (MRPL41) enhances p53 stability and contributes to p53-induced apoptosis in response to growth-inhibitory conditions such as actinomycin D treatment and serum starvation. An analysis of MRPL41 expression in paired normal and tumor tissues revealed lower expression in tumor tissue. Ectopic MRPL41 expression resulted in inhibition of the growth of cancer cells in tissue culture and tumor growth in nude mice. We discovered that MRPL41 protein is localized in the mitochondria, stabilizes the p53 protein, and enhances its translocation to the mitochondria, thereby inducing apoptosis. Interestingly, in the absence of p53, MRPL41 stabilizes the p27(Kip1) protein and arrests the cell cycle at the G1 phase. These results suggest that MRPL41 plays an important role in p53-induced mitochondrion-dependent apoptosis and MRPL41 exerts a tumor-suppressive effect in association with p53 and p27 (Kip1).
Yoo
Young A
YA
Graduate School of Medicine, Korea University College of Medicine, Anam Hospital, 126-1, 5ka, Anam-dong, Sungbuk-ku, Seoul 136-705, South Korea.
Kim
Mi Jin
MJ
Park
Jong Kuk
JK
Chung
Young Min
YM
Lee
Jong Hyeok
JH
Chi
Sung-Gil
SG
Kim
Jun Suk
JS
Yoo
Young Do
YD
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016193:G1 Phase / Q000502:physiology; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D012269:Ribosomal Proteins / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism* / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism* / Q000502:physiology*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D006131:Growth Inhibitors; C502654:MRPL41 protein, human; D024101:Mitochondrial Proteins; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27