Definition
MCJ is a member of the DNAJ family of co-chaperone proteins, whose expression is controlled by methylation of its associated CpG island. Reduced MCJ expression increases resistance to several commonly used cancer therapeutics by inducing expression of the ABCB1 drug-transport pump.
Characteristics
The MCJ gene maps at 13q14.1 and codes for a protein of 150 amino acids and 16–17 kDa. MCJ contains a highly conserved 70 amino acid DNAJ domain (or J-domain) located at the C terminus. J-domain proteins interact with the heat shock protein 70 (Hsp70) family of chaperone proteins and act as co-chaperones recruiting Hsp70 members to specific substrate proteins. MCJ has been shown to be a type II transmembrane protein localized in the Golgi network, with a cytoplasmic N terminus and a C terminus lying within the Golgi lumen.
The expression of MCJ is epigenetically (Epigenetics) regulated by methylation...
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References
Hatle KM, Neveu W, Dienz O et al (2007) MCJ promotes c-Jun degradation to prevent ABCB1 transporter expression. Mol Cell Biol 27:2952–2966
Lindsey JC, Lusher ME, Strathdee G et al (2006) Epigenetic inactivation of MCJ (DNAJD1) in malignant paediatric brain tumours. Int J Cancer 118:346–352
Shridhar V, Bible KC, Staub J et al (2001) Loss of expression of a new member of the DNAJ protein family confers resistance to chemotherapeutic agents used in the treatment of ovarian cancer. Cancer Res 61:4258–4265
Strathdee G, Vass JK, Oien KA et al (2005) Demethylation of the MCJ gene in stage III/IV epithelial ovarian cancer and response to chemotherapy. Gynecol Oncol 97:898–903
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Lindsey, J.C., Clifford, S.C. (2015). Methylation-Controlled J Protein. In: Schwab, M. (eds) Encyclopedia of Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46875-3_3685
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DOI: https://doi.org/10.1007/978-3-662-46875-3_3685
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