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Review
. 2018 Dec 12:11:122-126.
doi: 10.1016/j.omto.2018.11.002. eCollection 2018 Dec 21.

Exploiting Oncogenic Drivers along the CCNG1 Pathway for Cancer Therapy and Gene Therapy

Ahmad Al-Shihabi  1 , Sant P Chawla  1 , Frederick L Hall  2 , Erlinda M Gordon  1   2   3
Affiliations
Review

Exploiting Oncogenic Drivers along the CCNG1 Pathway for Cancer Therapy and Gene Therapy

Ahmad Al-Shihabi et al. Mol Ther Oncolytics. .
No abstract available

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Figures

Figure 1
Figure 1
Structure and Function Analysis of the Executive Cyclin G1 Gene Product Left: cyclin G1 functional domains. Cyclin G1 physically binds to the ser/thr protein phosphatase subunit designated 2A (PP2A) to activate a key regulatory oncoprotein, Mdm2. The Mdm2 oncoprotein forms a physical complex with the p53 tumor suppressor, thus inactivating its tumor suppressor function while additionally acting as a specific E3 ubiquitin ligase that is responsible for the ubiquitination and degradation of the p53 tumor suppressor protein. This dephosphorylation event is cyclin G1-dependent. Cyclin G1 also activates CDK5 and CDK2 to target and activate the c-Myc onco-protein. Right: dnG1 dominant-negative G1 (Killer Gene). The experimentally optimized cyclin G1 inhibitor, a cytocidal dominant-negative mutant construct of cyclin G1, is devoid of the “ubiquitinated” N terminus (proteolytic processing) as well as the first two helical segments (α1 and α 2) of the definitive Cyclin Box: characteristically arrayed in cyclins as a tandem set of helical segments, including two highly-conserved residues (asterisks) essential for cyclin-dependent kinase (Cdk) binding. The cytocidal dnG1 protein—which induces apoptosis in proliferative cells—retains the presumptive CDK contact points (helix α 3*, α 5*) and the structural domains attributed to PP2A, β’, and Mdm2 binding. Remarkably, small synthetic peptides (e.g., ELAS1 and 5 helix peptides) derived from structures or homologous interfaces contained within the cytocidal dnG1 protein have been reported to induce cell cycle blockade and apoptosis, respectively.
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