Nuclear cyclin D1: an oncogenic driver in human cancer
Open accessAbstract
Perturbations in the regulation of the core cell cycle machinery are frequently observed in human cancers. Cyclin D1 which functions as a mitogenic sensor and allosteric activator of CDK4/6, is one of the more frequently altered cell cycle regulators in cancers. Cyclin D1 is frequently overexpressed in cancers and its overexpression can be attributed to many factors including increased transcription, translation, and protein stability. Although cyclin D1 overexpression is clearly implicated in the affected cancers, overexpression of cyclin D1 is not sufficient to drive oncogenic transformation. Rather, emerging evidence suggests that nuclear retention of cyclin D1 resulting from altered nuclear trafficking and proteolysis is critical for the manifestation of its oncogenicity. This review provides a brief overview of current data documenting various mechanisms underlying aberrant cyclin D1 regulation in human cancers and their impact on neoplastic transformation. J. Cell. Physiol. 220: 292–296, 2009. © 2009 Wiley‐Liss, Inc.
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To exert an oncogenic effect in the nucleus, cyclin D1 must be aberrantly stabilized in conjunction with inhibition of its cytoplasmic relocalization.
“To exert an oncogenic effect in the nucleus, cyclin D1 must be aberrantly stabilized in conjunction with inhibition of its cytoplasmic relocalization (46), as exemplified by the situation for the nonphosphorylatable cyclin D1(T286A) variant used here (40).”
From A genome-wide screen reveals that Dyrk1A kinase promotes nucleotide excision repair by preventing aberrant overexpression of cyclin D1 and p21 (2023) · cites this paper as [46]
The Abstract and the section on aberrant nuclear accumulation (page not provided) link cyclin D1’s oncogenicity to nuclear retention, altered trafficking, and impaired proteolysis. The review describes this as emerging evidence and says nuclear retention may be a critical determinant; it does not establish that both stabilization and blocked cytoplasmic relocalization are invariably required, as “must” implies. (LLM, conf=0.86)
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- Authors
- Kim, J. K., & Diehl, J. A.
- Affiliations
- Abramson Cancer Center (US)
- Corresponding author
- Diehl, J. Alan
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2009-05-04
- Volume
- 220
- Issue
- 2
- Pages
- 292-296
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- PMC
- PMC2874239
- OpenAlex
- W2073482997
- Cited by
- 413
- References
- 63
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 3 · 2023: 16 · 2022: 20 · 2021: 25 · 2020: 26 · 2019: 21 · 2018: 17 · 2017: 23 · 2016: 25 · 2015: 26 · 2014: 34 · 2013: 42 · 2012: 37
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Leukemia and Lymphoma Society
- National Institutes of Health
- National Cancer Institute (R01CA093237, R01CA111360, CA 93237)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- cyclin D1, CDK4/6, oncogenic transformation, cell cycle regulation, cyclin D1 overexpression, nuclear retention, nuclear trafficking, proteolysis, protein stability, transcriptional regulation, translational regulation, human cancer
- MeSH terms
- Animals, Carcinogens, Cell Cycle, Cell Nucleus, Cell Transformation, Neoplastic, Humans, Neoplasms, Signal Transduction, Gene Expression Regulation, Neoplastic, Cyclin D1, Genomic Instability, Protein Kinase Inhibitors, Cyclin-Dependent Kinase 4
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