Cyclin, ubiquitination

Skowyea, D., et al.. Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrrl and Rbxl. Science, 1999, 284(5414), 662-5. 

Lahav-Baratz, S., Sudakin, V., Ruderman, J.V. and Hershko, A. (1995). Reversible phosphorylation controls the activity of cyclosome-associated cyclin-ubiquitin ligase. Proc. Natl. Acad. Sci. USA 92, 9303-9307. 

Morgan, T.H. (1911). Random segregation versus coupling in Mendelian inheritance. Science 34, 384. Murray, A. (1995). Cyclin ubiquitinization the destructive end of mitosis. Cell 81,149-152. 

APC is active from mid-M phase (anaphase) to the end of G1 phase and required for disconnecting sister chromatids and exit from M-Phase to Gl. The complex mediates the ubiquitination of Securin and Cyclin B. Degradation of these proteins, which block mitotic progression, promotes anaphase onset and exit from mitosis. 

King RW, Peters JM, Tugendreich S, Rolfe M, Hieter P, Kirschner MW 1995 A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell 81 279-288... 

Seino, H., Kishi, T., Nishitani, H., and Yamao, F. Two ubiquitin-conjugating enzymes, UbcPl/Ubc4 and UbcP4/Ubcll, have distinct functions for ubiquitination of mitotic cyclin. Mol Cell Biol 2003, 23, 3497-505. 

Townsley, F. M., Aristarkhov, A., Beck, S., Hershko, A., and Ruderman, J. V. Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase. Proc. Natl. Acad. Sei. USA 1997, 94, 2362-67. 

Seueert, W., Butcher, B., and Jentsch, S. Role of a ubiquitin-conjugating enzyme in degradation of S- and M-phase cyclins. Nature 1995, 373, 78-81. 

How does phosphorylation of the substrate control ubiquitination. In the case of protein such as c-jun, phosphorylation perhaps masks a signal in the substrate recognized by the E3 ligase such that the substrate is unavailable for ubiquitination. In contrast, in those substrates that become susceptible to degradation after phosphorylation such as yeast cyclins, it is probable that phosphorylation unmasks a sequence or tertiary structure in the substrate, which the E3 ligase can recognize for ubiquitination. 

Phosphorylation of ubiquitin ligases could have inhibitory effect as well. In the fission yeast Schizosaccharomyces pombe, PKA blocks APC activity. Moreover, the inhibitory effect of PKA seems to be dominant over the stimulatory effect of the polo-like kinase. Even if APC has been activated by polo-like kinase, addition of mammalian PKA to APC-containing fractions inhibits ubiquitination of the substrate cyclin... 

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