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PMID: 10825210 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

The oncoprotein kinase chaperone CDC37 functions as an oncogene in mice and collaborates with both c-myc and cyclin D1 in transformation of multiple tissues.

Molecular and cellular biology ·Vol. 20 ·No. 12 ·2000-06-00 ·Pages 4462-73

Stepanova L, Finegold M, DeMayo F, Schmidt EV, Harper JW

Abstract

CDC37 encodes a 50-kDa protein that targets intrinsically unstable oncoprotein kinases including Cdk4, Raf-1, and v-src to the molecular chaperone Hsp90, an interaction that is thought to be important for the establishment of signaling pathways. CDC37 is required for proliferation in budding yeast and is coexpressed with cyclin D1 in proliferative zones during mouse development, a finding consistent with a positive role in cell proliferation. CDC37 expression may not only be required to support proliferation in cells that are developmentally programmed to proliferate but may also be required in cells that are inappropriately induced to initiate proliferation by oncogenes. Here we report that mouse mammary tumor virus (MMTV)-CDC37 transgenic mice develop mammary gland tumors at a rate comparable to that observed previously in MMTV-cyclin D1 mice. Moreover, CDC37 was found to collaborate with MMTV-c-myc in the transformation of multiple tissues, including mammary and salivary glands in females and testis in males, and also collaborates with cyclin D1 to transform the female mammary gland. These data indicate that CDC37 can function as an oncogene in mice and suggests that the establishment of protein kinase pathways mediated by Cdc37-Hsp90 can be a rate-limiting event in epithelial cell transformation.

MeSH Terms
Animals Cell Cycle Proteins/genetics,metabolism Cell Transformation, Neoplastic Cyclin D1/genetics,metabolism Drosophila Proteins Female Gene Expression Regulation, Neoplastic Genes, myc Mice Mice, Transgenic Molecular Chaperones Oncogene Proteins/genetics,metabolism
Chemicals
Cdc37 protein, mouse Cell Cycle Proteins Drosophila Proteins Molecular Chaperones Oncogene Proteins Cyclin D1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Stepanova L
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Finegold M
DeMayo F
Schmidt E V
Harper J W
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.12.4462-4473.2000
Published
2000-06-00
Pages
4462-73
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC85814
Subset
IM
Grants
NIGMS NIH HHS · R01 GM054137 · United States
NIGMS NIH HHS · GM54137 · United States
External Links
PubMed source DOI: 10.1128/MCB.20.12.4462-4473.2000 PMC Full Text View journal details
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