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PMID: 10465786 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival.

Genes & development ·Vol. 13 ·No. 16 ·1999-08-15 ·Pages 2087-97

Okano HJ, Park WY, Corradi JP, Darnell RB

Abstract

Paraneoplastic cerebellar degeneration (PCD) is a disorder in which breast or ovarian tumors express an onconeural antigen termed cdr2, which normally is expressed in cerebellar Purkinje neurons. This leads to an immune response to cdr2 that is associated with tumor immunity and autoimmune cerebellar degeneration. We have found that cdr2, a cytoplasmic protein harboring a helix-leucine zipper (HLZ) motif, interacts specifically with the HLZ motif of c-Myc. Both proteins colocalize in the cytoplasm of adult cerebellar Purkinje neurons, and coimmunoprecipitate from tumor cell lines and cerebellar extracts. cdr2 down-regulates c-Myc-dependent transcription in cotransfection assays, and redistributes Myc protein in the cytoplasm. Disease antisera from six of six PCD patients specifically blocked the interaction between cdr2 and c-Myc in vitro. These data indicate that cdr2 normally sequesters c-Myc in the neuronal cytoplasm, thereby down-regulating c-Myc activity, and suggest a mechanism whereby inhibition of cdr2 function by autoantibodies in PCD may contribute to Purkinje neuronal death.

MeSH Terms
Animals Autoantibodies/immunology Autoantigens/genetics,immunology,metabolism Cell Survival Cytoplasm/metabolism DNA-Binding Proteins/genetics,immunology,metabolism Down-Regulation HeLa Cells Humans Leucine Zippers Male Mice Paraneoplastic Syndromes/immunology Proto-Oncogene Proteins c-myc/metabolism Purkinje Cells/cytology,metabolism Rats Rats, Sprague-Dawley Transcription, Genetic Tumor Cells, Cultured
Chemicals
Autoantibodies Autoantigens DNA-Binding Proteins Proto-Oncogene Proteins c-myc
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Okano H J
Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York 10021 USA.
Park W Y
Corradi J P
Darnell R B
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.13.16.2087
Published
1999-08-15
Pages
2087-97
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316965
Subset
IM
Grants
NCRR NIH HHS · M01 RR000102 · United States
NIGMS NIH HHS · T32 GM007982 · United States
External Links
PubMed source DOI: 10.1101/gad.13.16.2087 PMC Full Text View journal details
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