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Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function.
Open accessAbstract
The D-type cyclin-dependent kinases CDK4 and CDK6 are complexed with many small cellular proteins (p14, p15, p16, p18, and p20). We have isolated cDNA sequences corresponding to the MTS2 genomic fragment that encodes the CDK4- and CDK6-associated p14 protein. By use of a yeast interaction screen to search for CDK6-interacting proteins, we have also identified an 18-kD human protein, p18, that is a homolog of the cyclin D-CDK4 inhibitors p16 (INK4A/MTS1) and p14 (MTS2/INK4B). Both in vivo and in vitro, p18 interacts strongly with CDK6, weakly with CDK4, and exhibits no detectable interaction with the other known CDKs. Recombinant p18 inhibits the kinase activity of cyclin D-CDK6. Distinct from the p21/p27 family of CDK inhibitors that form ternary complexes with cyclin-CDKs, only binary complexes of p14, p16, and p18 were found in association with CDK4 and/or CDK6. Ectopic expression of p18 or p16 suppresses cell growth with a correlated dependence on endogenous wild-type pRb.
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Weinberg, R. A. (1995) · Cell · doi:10.1016/0092-8674(95)90385-2 · Cited by 4,862
Cell cycle, CDKs and cancer: a changing paradigm
Malumbres, M., & Barbacid, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2602 · Cited by 3,957
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Metadata
- Authors
- Guan, K. L., Jenkins, C. W., Li, Y., Nichols, M. A., Wu, X., O'Keefe, C. L., Matera, A. G., & Xiong, Y.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1994-12-15
- Volume
- 8
- Issue
- 24
- Pages
- 2939-2952
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2033156691
- Cited by
- 714
- References
- 5
- Type
- posted content
- Language
- en
- Open access
- diamond
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- CoChat. (2026). Citation check: Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function. https://app.cochat.ai/papers/10.1101/gad.8.24.2939
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- Guan, K. L., Jenkins, C. W., Li, Y., Nichols, M. A., Wu, X., O'Keefe, C. L., Matera, A. G., & Xiong, Y. (1994). Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function. Genes & Development. https://doi.org/10.1101/gad.8.24.2939
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