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. 2008 Aug 13;36(16):5391–5404. doi: 10.1093/nar/gkn522

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© 2008 The Author(s)

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 7. — miR-16 family modulates G1/S transition by regulating Cdk4/6-cyclin D complexes and Cdk2-cyclin E complexes. The G1/S phase transition is regulated primarily by D-type Cyclins (D1, D2 or D3) in complex with CDK4/CDK6, and E-type Cyclins (E1 or E2) in complex with CDK2. These complexes cooperate in phosphorylating and preventing Rb binding to E2F, thus activating E2F-mediated transcription and driving cells from G1 into S phase. miR-16 family control the expression levels of Cyclin D1, Cyclin D3, Cyclin E1 as well as CDK6, inactivate Cdk2/4/6 kinases, and thus prevent phosphorylation of Rb proteins. Moreover, miR-16 can induce apoptosis by downregulation of antiapoptosis protein Bcl-2.