Molecular interactions of Bcl-2 and Bcl-xL with mortalin: identification and functional characterization.
Bcl-2 family of proteins consists of both pro-apoptotic and anti-apoptotic members that control cellular apoptosis. They predominantly reside in the mitochondria and control the release of apoptotic factors from the mitochondria to the cytosol by regulating its membrane potential and opening the PT (permeability transition) pore. Here we report bioinformatics and biochemical evidence to demonstrate the interaction between Bcl-2 and Bcl-xL with a stress chaperone, mortalin. We demonstrate that such interaction results in the abrogation of mortalin-p53 interaction leading to nuclear translocation and transcriptional reactivation of p53 function that results in an induction of senescence in cancer cells.
*National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba Science City 305-8562, Japan.
Nishant
N
Saxena
†Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi 110016, India.
Shashank P
SP
Katiyar
*National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba Science City 305-8562, Japan.
Ye
Y
Liu
†Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi 110016, India.
Abhinav
A
Grover
*National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba Science City 305-8562, Japan.
Ran
R
Gao
†Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi 110016, India.
Durai
D
Sundar
*National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba Science City 305-8562, Japan.
Sunil C
SC
Kaul
*National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba Science City 305-8562, Japan.
Renu
R
Wadhwa
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013816:Thermodynamics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051020:bcl-X Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C494811:BCL2L1 protein, human; D018840:HSP70 Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; C080352:mortalin