ArticleCell cycle (Georgetown, Tex.)2013
Cyclin-dependent kinase 4 may be expressed as multiple proteins and have functions that are independent of binding to CCND and RB and occur at the S and G 2/M phases of the cell cycle.
Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 22 citations in OpenAlex.
- Updating mRNA variants of the human RSK4 gene and their expression in different stressed situations.Heliyon · 2024Article
- At elevated temperatures, heat shock protein genes show altered ratios of different RNAs and expression of new RNAs, including several novel HSPB1 mRNAs encoding HSP27 protein isoforms.Experimental and therapeutic medicine · 2021Article
- ACTB and GAPDH appear at multiple SDS-PAGE positions, thus not suitable as reference genes for determining protein loading in techniques like Western blotting.Open life sciences · 2021Article
- About three-fourths of mouse proteins unexpectedly appear at a low position of SDS-PAGE, often as additional isoforms, questioning whether all protein isoforms have been eliminated in gene-knockout cells or organisms.Protein science : a publication of the Protein Society · 2020Article
- Targeted Gene Expression Profile Reveals CDK4 as Therapeutic Target for Selected Patients With Adrenocortical Carcinoma.Frontiers in endocrinology · 2020Article
- Down-regulation of POTEG predicts poor prognosis in esophageal squamous cell carcinoma patients.Molecular carcinogenesis · 2018Article
- While it is not deliberate, much of today's biomedical research contains logical and technical flaws, showing a need for corrective action.International journal of medical sciences · 2018Review
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- It Is Imperative to Establish a Pellucid Definition of Chimeric RNA and to Clear Up a Lot of Confusion in the Relevant Research.International journal of molecular sciences · 2017Review
- Direct repression of the oncogene CDK4 by the tumor suppressor miR-486-5p in non-small cell lung cancer.Oncotarget · 2016Article
- The helicase-like transcription factor (HLTF) in cancer: loss of function or oncomorphic conversion of a tumor suppressor?Cellular and molecular life sciences : CMLS · 2016Review
- Article
- JMJD3 promotes SAHF formation in senescent WI38 cells by triggering an interplay between demethylation and phosphorylation of RB protein.Cell death and differentiation · 2015Article
- To Know How a Gene Works, We Need to Redefine It First but then, More Importantly, to Let the Cell Itself Decide How to Transcribe and Process Its RNAs.International journal of biological sciences · 2015Review
- Article
- The other side of the coin: the tumor-suppressive aspect of oncogenes and the oncogenic aspect of tumor-suppressive genes, such as those along the CCND-CDK4/6-RB axis.Cell cycle (Georgetown, Tex.) · 2014Review
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Authors and funding
11 authors at 5 institutions in 4 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Cyclin-dependent kinase 4 (CDK4) is known to be a 33 kD protein that drives G 1 phase progression of the cell cycle by binding to a CCND protein to phosphorylate RB proteins. Using different CDK4 antibodies in western blot, we detected 2 groups of proteins around 40 and 33 kD, respectively, in human and mouse cells; each group often appeared as a duplet or triplet of bands. Some CDK4 shRNAs could decrease the 33 kD wild-type (wt) CDK4 but increase some 40 kD proteins, whereas some other shRNAs had the opposite effects. Liquid chromatography-mass spectrometry/mass spectrometry analysis confirmed the existence of CDK4 isoforms smaller than 33 kD but failed to identify CDK4 at 40 kD. We cloned one CDK4 mRNA variant that lacks exon 2 and encodes a 26 kD protein without the first 74 amino acids of the wt CDK4, thus lacking the ATP binding sequence and the PISTVRE domain required for binding to CCND. Co-IP assay confirmed that this ΔE2 protein lost CCND1- and RB1-binding ability. Moreover, we found, surprisingly, that the wt CDK4 and the ΔE2 could inhibit G 1-S progression, accelerate S-G 2/M progression, and enhance or delay apoptosis in a cell line-specific manner in a situation where the cells were treated with a CDK4 inhibitor or the cells were serum-starved and then replenished. Hence, CDK4 seems to be expressed as multiple proteins that react differently to different CDK4 antibodies, respond differently to different shRNAs, and, in some situations, have previously unrecognized functions at the S-G 2/M phases of the cell cycle via mechanisms independent of binding to CCND and RB.
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