P27 cis-regulatory element

p27 cis-regulatory element
Predicted secondary structure and sequence conservation of p27_CRE
Identifiers
Symbol	p27_CRE
Rfam	RF00454
Other data
RNA type	Cis-reg
Domain(s)	Eukaryota
SO	0000204

The p27 cis-regulatory element is a structured G/C rich RNA element which is involved in controlling cell cycle regulated translation of the p27^kip protein in human cells.^[1]

The p27^kip1 protein is involved in cell cycle regulation and belongs to the Cip/Kip family of cyclin dependent kinase(CDK)inhibitors.^[2] These inhibitors possess an N-terminal CDK-inhibitory domain which binds to the ATP binding pocket of the kinase and modulates its function.^[3]

This p27 cis-regulatory element is 114 nucleotides in length and is located at the very 5' end of the 5'UTR of the p27 mRNA. It contains a small open reading frame (ORF) of 29 amino acids which is preceded by and overlaps with a G/C-rich hairpin domain. This hairpin domain is predicted to form multiple stable stem loops with similar free energy. Both the open reading frame and the stem loop elements contribute to cell cycle-regulated translation of the p27 mRNA.^[1]

The structure of the G/C rich element appears to be important to its regulatory function as replacement of the G/C rich region with an unstructured sequence has a greater effect on regulation of translation than a simple deletion of part of the G/C rich region. It has been suggested that cell cycle specific binding proteins may favour one of the predicted structures in the G/C region thereby promoting conformational states which could regulate downstream translation.^[1]

This element was initially characterised in human cells but has predicted homologs in mice and chickens.^[1]

References

1. ^ ^{a b c d} Gopfert, U; Kullmann M, Hengst L (2003). "Cell cycle-dependent translation of p27 involves a responsive element in its 5'-UTR that overlaps with a uORF". Hum Mol Genet 12 (14): 1767–1779. doi:10.1093/hmg/ddg177. PMID 12837699. 
2. ^ Polyak K, Kato JY, Solomon MJ, et al. (January 1994). "p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest". Genes Dev. 8 (1): 9–22. doi:10.1101/gad.8.1.9. PMID 8288131. http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=8288131. 
3. ^ Russo AA, Jeffrey PD, Patten AK, Massagué J, Pavletich NP (July 1996). "Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex". Nature 382 (6589): 325–31. doi:10.1038/382325a0. PMID 8684460. 

External links

• Rfam page for p27 cis-regulatory element