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The specific and rapid destruction of cyclins A and B during mitosis is their most remarkable property. A short peptide motif of approximately 10 amino acids near the N‐terminus, known as the destruction box, is absolutely required for programmed proteolysis. In this paper we show that although the destruction box is necessary for the degradation of cyclin A, it is not sufficient. Mutant versions of cyclin A that cannot form complexes with p34cdc2 are stable, which we interpret to mean that this cyclin must bind to p34cdc2 in order to undergo programmed proteolysis. Thus, N‐terminal fragments of cyclin A containing little more than the destruction box and its surroundings are indestructible. p34cdc2 binding also appears to be required for the destruction of cyclin B2. In contrast, cyclin B1 does not require p34cdc2 binding for specific proteolysis. The systems for the proteolysis of cyclins A, B1 and B2 thus appear to show important differences in the way they recognize their substrates.

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The brain tumor glioblastoma remains one of the most aggressive and devastating tumors despite decades of effort to find more effective treatments. A hallmark of glioblastoma is the constitutive activation of the NF-κB signaling pathway, which regulates cell proliferation, inflammation, migration, and apoptosis. The prolyl isomerase Pin1 has been found to bind directly to the NF-κB protein, p65, and cause increases in NF-κB promoter activity in a breast cancer model. We now present evidence that this interaction occurs in glioblastoma and that it has important consequences on NF-κB signaling. We demonstrate that Pin1 levels are enhanced in primary glioblastoma tissues compared to controls, and that this difference in Pin1 expression affects the migratory capacity of glioblastoma-derived cells. Pin1 knockdown decreases the amount of activated, phosphorylated p65 in the nucleus, resulting in inhibition of the transcriptional program of the IL-8 gene. Through the use of microarray, we also observed changes in the expression levels of other NF-κB regulated genes due to Pin1 knockdown. Taken together, these data suggest that Pin1 is an important regulator of NF-κB in glioblastoma, and support the notion of using Pin1 as a therapeutic target in the future.