Cell cycle question - CKIs - (Apr/26/2005 )
Here's a silly question that we have been discussing in my lab and I'm hoping someone will be able to shed some light on it.
Does the actual total protein levels of the various CKI's (p27, p21, p19, p14, etc) fluctuate? or is it only the phosphorylated levels that increase/decrease through cell cycle progression?
Not a silly question at all! I don't know about the others but the total protein levels of p21 do rise due to an increase in transcription (and also a decrease in protein degradation-I think? not entirely sure about this second part). These inhibiters are also regulated by sub-cellular localisation, exclusion from the nucleus etc.
It sound like a lot of making and breaking up of protein just to keep the cells cycling and it would be more economical for the cell just to phosphorylate a protein. However, it is important to keep in mind that for mammalian cells being in cycle is the exception not the rule! I think growing cells in culture often gives us a false idea of the "usual" state of the cell. Most of the cells in the body are terminally differentiated and never go into cycle! Being growth arrested is normal for cells. Even stem cells are usually quiescent and will only divide when given specific signals to do so.
CKI maintains CDK/cyclin complex inactive, until this complex is required for cell cycle progression. Then there is a phosphorylation of the CKI, and this is the signal for ubiquitinylation of the CKI, and by the way, CKI is then proteasome destructed.
So i assume levels of the various inhibitors fluctuate through the cell cycle...