A cyclin-dependent kinase inhibitor inducing cancer cell differentiation: Biochemical identification using Xenopus egg extracts
SCIE
SCOPUS
- Title
- A cyclin-dependent kinase inhibitor inducing cancer cell differentiation: Biochemical identification using Xenopus egg extracts
- Authors
- Rosania, GR; Merlie, J; Gray, N; Chang, Young-Tae; Schultz, PG; Heald, R
- Date Issued
- 1999-04
- Publisher
- NATL ACAD SCIENCES
- Abstract
- Cellular differentiation is a complex process involving growth arrest, exit from the cell cycle, and expression of differentiated cell-type specific functions. To identify small molecules promoting this process, a chemical library was screened by using a myeloid leukemic cell line that retained the potential to differentiate in culture. In the presence of a purine derivative, aminopurvalanol (AP), cells acquired phenotypic characteristics of differentiated macrophages and became arrested in the cell cycle with a 4N DNA content. AP also inhibited mitosis in Xenopus egg extracts, suggesting that it acted on an evolutionarily conserved cell cycle regulatory pathway, Affinity chromatography and biochemical reconstitution experiments with Xenopus egg extracts identified cyclin-dependent kinase (CDK) 1-cyclin B as a target of the compound. Although AP potently inhibited immunoprecipitates of both human CDK1 and CDK2 from human leukemic cell extracts, our results indicate that the compound preferentially targets the G(2)/M-phase transition in vivo.
- Keywords
- PROMYELOCYTIC LEUKEMIA; RETINOIC ACID; S-PHASE; PROTEINS; MITOSIS; GROWTH; YEAST; P21
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/50276
- DOI
- 10.1073/pnas.96.9.4797
- ISSN
- 0027-8424
- Article Type
- Article
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 96, no. 9, page. 4797 - 4802, 1999-04
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- There are no files associated with this item.
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