N-Terminal polyubiquitination of the ARF tumor suppressor, a natural lysine-less protein.
Ubiquitin-dependent proteolysis by proteasomes generally depends upon the conjugation of polyubiquitin chains to lysine epsilon-NH(2) groups within the targeted proteins. However, engineered lysine-less mutants of certain viral and cellular proteins can undergo polyubiquitination at their N-termini. Is N-terminal polyubiquitination a physiologic process, and how many cellular proteins can be targeted for proteasomal degradation through this mechanism? Recent work indicates that the turnover of the endogenous lysine-less human ARF tumor suppressor protein and its mouse Arf counterpart (containing a single, non-conserved lysine residue) is regulated in this manner.
Howard Hughes Medical Institute, Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Mei-Ling
ML
Kuo
Willem
W
den Besten
Charles J
CJ
Sherr
D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational
C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; D008239:Lysine