cdr2

Antisera positive for the Yo antibody was obtained from PCD patients and used by several groups to clone a target antigen termed cdr2. Immunity to the cdr2 antigen in gynecologic tumors is associated with effective anti-tumor immunity; 45/52 (87%) of patients with the Yo antibody and gynecologic cancer have limited tumors.

Importantly, expression of cdr2 is not limited to patients with gynecologic cancer and PCD as originally thought (Furneaux HM, Rosenblum MK, Dalmau J, Wong E, Woodruff P, Graus F, Posner JB. N Engl J Med. 1990 Jun 28;322(26):1844-51). We have found that expression is common in the general population of cancer patients: ~60% of neurologically normal ovarian cancer and ~25% of neurologically normal breast cancer patients (Darnell JC, Albert ML and Darnell RB. Cancer Res, 60, 2136-2139, 2000).

In normal tisssues, cdr2 antigen expression appears to be tightly restricted to specific areas of the brain (most prominantly Purkinje neurons in the cerebellum), and to testis. Interestingly, this restricted pattern of expression is evident using PCD antisera to probe Western blots and by immunohistochemistry, but is not evident at the RNA level, as cdr2 mRNA appears to be widely expressed (Corradi JP, Yang CW, Darnell JC, Dalmau J and Darnell RB. J Neurosci, 17:1406-1415, 1997). We are currently actively studying this discrepancy. The cdr2 gene encodes a protein of predicted Mr 52kD that harbors an extended amphipathic helix-leucine zipper domain in its N-terminal one-third, and a unique sequence of unknown function in its C-terminal two-thirds, suggesting separate dimerization and functional domains. The disease epitope has been mapped using Yo antisera, and localizes to the N-terminal leucine zipper domain. The cdr2 antigen localizes to the cell soma and cytoplasmic fractions of neurons. We have found that cdr2 interacts with the c-myc protein in Purkinje neurons, both by co-IP and in functional assays, where it downregulates the ability of c-myc to induce E-box dependent transcription (Okano HJ, Park W, Corradi JP and Darnell RB. Genes & Dev, 13:2087-2097, 1999.). We are currently exploring cdr2 function in the brain and in tumor cells.