A Novel Link Between SUMO Modification and Cancer Metastasis

Loss of SUMO1 in mice affects RanGAP1 localization and formation of PML nuclear bodies, but is not lethal as it can be compensated by SUMO2 or SUMO3

“…This has important implications for any effort to develop rational approaches for targeting the SUMO pathway. Based on recent findings showing an association between sumoylation and carcinogenesis and metastasis (Baek, 2006;Cheng et al, 2006;Katayama et al, 2007;Kim and Baek, 2006;Moschos and Mo, 2006;Seeler et al, 2007;Wu and Mo, 2007), targeting the SUMO pathway for cancer therapy has been proposed (Mo and Moschos, 2005). The fact that SUMO family members can substitute for each other suggests that components of the pathway other than SUMO, perhaps the deconjugation enzymes, might be the most effective targets for rational drug development.…”

“…Modification of proteins with SUMO, or sumoylation, regulates many essential cellular activities, including nucleocytoplasmic transport, transcription, and maintenance of genome integrity (Geiss-Friedlander and Melchior, 2007;Gill, 2004;Girdwood et al, 2004;Hay, 2005;Johnson, 2004), and has been implicated in tumorigenesis and metastasis (Baek, 2006;Seeler et al, 2007). A large number of proteins have now been shown to be sumoylated, with the outcome varying depending on the target protein.…”

β-catenin takes a HIT

“…As exemplified by studies on the regulation of the metastasis suppressor gene KAI1, Pontin and Reptin in combination with the histone acetyltransferase Tip60 and β-catenin, respectively, form distinct activating or repressing complexes on the KAI1 promoter. 59 Sumoylation of Reptin 70 and Pontin 71 appear to be of important regulatory function. Further roles for Pontin and Reptin have been established in the maturation of small nucleolar RNAs 72 and in the organization of centrosomal protein complexes.…”

Regulation of the sumoylation system in gene expression

“…In addition, hypoxia can induce the expression of SUMO-1 [15] and an RWD-containing sumoylation enhancer (RSUME) that functions to promote protein sumoylation (see the next section for details) [16]. The elevated expression of Ubc9 has been observed in a number of human malignancies, such as lung adenocarcinoma, melanoma, breast and ovarian carcinoma [17]. Despite these interesting findings, little is known about the molecular mechanisms responsible for the regulation of the expression of the sumoylation system.…”