Protein and Nucleic Acid Degradation A set of enzymes targets a protein for degradation by tagging it with an ~70 amino acid protein called ubiquitin.

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Presentation transcript:

Protein and Nucleic Acid Degradation A set of enzymes targets a protein for degradation by tagging it with an ~70 amino acid protein called ubiquitin. The ubiquitin tag is recognized by a large protein machine called a proteasome. Upon entering the proteasome, the protein is unfolded and hydrolysed (degraded). Ubiquitin molecules are highly resistant to the proteasome and can be recycled.

Skp1-Cdc53-F box (+Rbx+cdc34(E2))

Suggest 2 possibilities how cln and cdc34 interact. Which is more likely ?

Anaphase Promoting Complex/ Cyclosome

Fzr activation of the cyclosome is inhibited by cdk1-cyclin B kinase activity 125 I-Cyclin B (Ub) n 125 I-Cyclin B Cyclosome Fzr Cdk1-cyclin B1 Staurosporine

Cdk1-cyclin B phosphorylation of fzr prevents fzr from activating the cyclosome I-Cyclin B Incubation II fzr CS Incubation I fzr CS cdk I-Cyclin B (Ub) n

APC Checkpoint cdk1 Cyclin B Fzy Checkpoint Fzr Polo Prophase Emi

APC cdk1 Cyclin B Fzy Checkpoint Fzr Polo Metaphase

APC cdk1 Cyclin B Fzr Fzy Fzr Fzy Anaphase Polo cdc14 Metaphase

APC cdk2 Cyclin A Fzr G1 Emi Fzr S

APC Checkpoint cdk1 Cyclin B Fzy Checkpoint Fzr Polo Prophase Emi

APC cdk1 Cyclin B Fzy Checkpoint Fzr Polo Metaphase

APC cdk1 Cyclin B Fzr Fzy Fzr Fzy Anaphase Polo cdc14 Metaphase

Substrates of the APC/C Cyclin APrometaphase Cyclin B (1,2,3)Metaphase-anaphase-G1 Securin (Pds1, Cut2)Metaphase-anaphase -G1 XkidMetaphase-anaphase -G1 AseITelophase (?) Cdc6 (metazoan)G1 Geminin?-G1 Fzy (cdc20) Telophase-G1 Polo (plk1, cdc5) Ubch10 Telophase

Hours after release from nocodazole KAA-DM KAA WT DM Securin degradation is mediated both by a d-box and by a KEN-box

Metaphase Anaphase Telophase Cytokinesis