User:Iris To/Retinoblastoma Protein Regulation
From Proteopedia
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==3D Structure== | ==3D Structure== | ||
| - | [[ | + | [[1o9k]] with E2F<br /> |
| - | [[ | + | [[1h25]] with Cdk2/Cyclin A<br /> |
==References== | ==References== | ||
{{Reflist}} | {{Reflist}} | ||
Revision as of 23:49, 26 November 2011
Contents |
Retinoblastoma Protein
The retinoblastoma protein (Rb) is a suppressor protein, also known as a tumor suppressor, involved in negative regulation of the cell cycle[1] due to its ability to bind the transcription factor E2F[2]. It acts as a cell cycle checkpoint during the G1 phase, determining if the cell cycle should continue or stop. In its normal state, Rb is activated, which prevents the cell cycle to continue because it can recruit transcriptional co-repressors, blocking transcription[1]. Rb is deactivated after being phosphorylated by Cyclin-dependent kinases (Cdks)[3], and thus cannot associate factors that inhibit transcription factors that allow the cell cycle to continue. Unregulated deactivation of Rb can lead to uncontrolled growth of cells, which is why studying this protein is important in cancer research.
Regulation of Rb
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| 3n5u, resolution 3.20Å () | |||||||
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| Ligands: | , | ||||||
| Gene: | PPP1A, PPP1CA (Homo sapiens) | ||||||
| Activity: | Phosphoprotein phosphatase, with EC number 3.1.3.16 | ||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
From previous studies, it has been determined that the phosphorylation state and activity of Rb are controlled by a balance of kinase and phosphatase activity[2], in which Cdks phosphorylate Rb from late G1 to mitosis and the enzyme protein phosphatase 1 (PP1c) dephosphorylates Rb for mitotic exit[3]. An enzyme-docking site for PP1c was determined to overlap with the docking site for Cdks through a crystal structure, initiating studies on phosphatase and kinase competition for the docking site.
Structure
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Importance
3D Structure
1o9k with E2F
1h25 with Cdk2/Cyclin A
References
- ↑ Lee C, Chang JH, Lee HS, Cho Y. Structural basis for the recognition of the E2F transactivation domain by the retinoblastoma tumor suppressor. Genes Dev. 2002 Dec 15;16(24):3199-212. PMID:12502741 doi:10.1101/gad.1046102
- ↑ Stone EM, Yamano H, Kinoshita N, Yanagida M. Mitotic regulation of protein phosphatases by the fission yeast sds22 protein. Curr Biol. 1993 Jan;3(1):13-26. PMID:15335873
- ↑ Hirschi A, Cecchini M, Steinhardt RC, Schamber MR, Dick FA, Rubin SM. An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein. Nat Struct Mol Biol. 2010 Sep;17(9):1051-7. Epub 2010 Aug 8. PMID:20694007 doi:10.1038/nsmb.1868
