Phosphorylation- and ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor Far1p in budding yeast

Abstract

Cyclin-dependent kinase inhibitors (CKIs

Interaction with cyclin-dependent kinases and PCNA modulates proteasome-dependent degradation of p21

“…This hypothesis is supported by our observation that the point mutations introduced into this p21 CDK7 mutant do not a ect other properties of p21, including the association with other partners such as PCNA, the targeting to the nucleus and the capacity to cause G1 and G2 growth arrest in DLD1 cells (Cayrol et al, 1998). Binding of p21 to cyclin/CDK complexes may therefore play an active role in proteasome-dependent degradation of p21, similarly to what has been found for the related human CKI p27 (Shea et al, 1997;Vlach et al, 1997) or the yeast CKIs Sic1p (Verma et al, 1997) and Far1p (Henchoz et al, 1997). Proteasome-mediated degradation of these three CKIs has been shown to be dependent on association with active G1 cyclin/CDK complexes and on phosphorylation of these inhibitors.…”

“…In addition, p21 has been found to be ubiquitinated in vivo (Maki and Howley, 1997) suggesting that p21 levels may be regulated by the ubiquitin-proteasome pathway. This system plays a key role in cell cycle control by regulating the abundance of a number of regulatory proteins, including the human CKI p27 (Pagano et al, 1995) and the yeast CKIs Sic1p (Verma et al, 1997) and Far1p (Henchoz et al, 1997). Although p21 was initially thought not to be regulated by the proteasome-dependent pathway (Pagano et al, 1995), more recent studies indicate that proteasome mediated proteolysis may play a role in the regulation of p21 abundance (Blagosklonny et al, 1996;Maki and Howley, 1997).…”

Two F‐box/WD‐repeat proteins Pop1 and Pop2 form hetero‐ and homo‐complexes together with cullin‐1 in the fission yeast SCF (Skp1‐Cullin‐1‐F‐box) ubiquitin ligase

“…Interestingly, Rum1 also needs to be phosphorylated by Cdc2 for degradation K Kominami et al 730 Genes to Cells (1998) ( Benito et al 1998). Phosphorylation-dependent degradation of substrates via the F-box proteins also takes place in budding yeast SCF (Willems et al 1996;Feldman et al 1997;Henchoz et al 1997;Skowyra et al 1997;Verma et al 1997). Given the presence of multiple phosphorylation sites in known substrates such as Cdc18, Rum1 and Sic1 (Jallepalli et al 1997(Jallepalli et al , 1998Verma et al 1997;Benito et al 1998), it is tempting to speculate that each of the two (or multiple) F-box proteins in a single SCF complex recognizes different CDK-phosphorylated sites in a coordinate manner, ensuring tight binding and targeting of substrates to the proteasome.…”

SCFCdc4-mediated Degradation of the Hac1p Transcription Factor Regulates the Unfolded Protein Response inSaccharomyces cerevisiae

“…In yeast, Cdc4p-dependent degradation of CDK inhibitors like Sic1p and Far1p and the DNA replication regulator Cdc6p require the activity of the cell cycle CDK Cdc28p (Henchoz et al, 1997: Verma et al, 1997Elsasser et al, 1999). In contrast, degradation of the transcriptional activator Gcn4 involves its phosphorylation by Srb10 or Pho85 kinases (Meimoun et al, 2000;Chi et al, 2001).…”