Disease relevance of Sumo1

• The present study investigates the regulation of small ubiquitin-related modifier-1 (SUMO-1) expression in response to hypoxia in adult mouse brain and heart [1].
• Generation of SUMO-1 modified proteins in E. coli: towards understanding the biochemistry/structural biology of the SUMO-1 pathway [2].
• Proteasome-independent disruption of PML oncogenic domains (PODs), but not covalent modification by SUMO-1, is required for human cytomegalovirus immediate-early protein IE1 to inhibit PML-mediated transcriptional repression [3].

High impact information on Sumo1

• Sumoylation of ICA512 by the E3 SUMO ligase PIASy, in turn, may reverse this process by decreasing the binding of ICA512 to STAT5 [4].
• Here, we demonstrate that the erythroid transcription factor GATA-1 is sumoylated in vitro and in vivo and map the single lysine residue involved in SUMO-1 attachment [5].
• Conjugation to SUMO is a reversible posttranslational modification that has been shown to regulate important transcription factors involved in cell proliferation, differentiation, and tumor suppression [5].
• Posttranslational modification of substrates by the small ubiquitin-like modifier, SUMO, regulates diverse biological processes, including transcription, DNA repair, nucleocytoplasmic trafficking, and chromosome segregation [6].
• The SUMO-specific protease SENP5 is required for cell division [6].

Chemical compound and disease context of Sumo1

• To target and identify UBL-modifying enzymes, we produced Nedd8, ISG15, and SUMO-1 in Escherichia coli and equipped them with a C-terminal electrophilic trap (vinyl sulfone [VS]) via an intein-based method [7].

Biological context of Sumo1

• In the ovary, the expression of SUMO-1 protein is suppressed around ovulation, in both the whole ovary and the granulosa cells, after gonadotropin treatment [8].
• The small ubiquitin-related modifier-1 (SUMO-1) with broad cellular expression has been implicated in a range of cellular processes, such as cell proliferation, differentiation, and apoptosis [9].
• In mouse, we found that Sumo1 is expressed in the developing lip and palate and that a Sumo1 hypomorphic allele manifests an incompletely penetrant orofacial clefting phenotype [10].
• The covalent modification of proteins by the small ubiquitin-like protein SUMO has been implicated in the regulation of numerous biological processes, including nucleocytoplasmic transport, genomic stability, and gene transcription [11].
• Striking SUMO-1 increases in the sex body of early-to-mid-pachytene spermatocytes correlated with timing of additional sex chromosome condensation [12].

Anatomical context of Sumo1

• Testicular expression of small ubiquitin-related modifier-1 (SUMO-1) supports multiple roles in spermatogenesis: silencing of sex chromosomes in spermatocytes, spermatid microtubule nucleation, and nuclear reshaping [12].
• Whereas SUMO-1 is detected in the testis, little is known about its reproductive role in males [12].
• During germ cell development, SUMO-1 was observed at low but detectable levels in the cytoplasm of spermatogonia and early spermatocytes [12].
• Testicular SUMO-1 expression supports its specific functions in inactivation of sex chromosomes during meiosis, spermatid microtubule nucleation, nuclear reshaping, and gene expression [12].
• Interestingly, knockdown of the SUMO-conjugating enzyme, Ubc9, severely compromises C2C12 muscle cell terminal differentiation [13].

Associations of Sumo1 with chemical compounds

• In contrast, another mutant of TDGb (TDGb(KR)) in which the lysine residue targeted for SUMO-1 conjugation is replaced with arginine retained the ability to bind SUMO-1 non-covalently [14].
• Additionally, when the ovulatory signal, the endogenous LH surge, is blocked in vivo by pentobarbitone sodium, the expression of SUMO-1 protein in granulosa cells is increased [8].
• Second, treatment with either PR antagonists or a cell permeable ceramide analog consistently increases SUMO-1 expression in parallel with an increase in apoptosis as well as a decrease in cell proliferation in periovulatory granulosa cells in vitro [9].
• Androgen receptor-positive Leydig, Sertoli, and some peritubular myoepithelial cells express SUMO-1, findings suggesting a role in modulating steroid action [12].
• These results indicated activation of SUMO-1 system in polyglutamine diseases and predicted its involvement in the pathology [15].

Other interactions of Sumo1

• PIAS3 induces SUMO-1 modification and transcriptional repression of IRF-1 [16].
• Instead, our data suggest that SUMO-mediated repression involves direct interaction of the DEAD-box protein DP103 with sumoylated SF-1 [17].
• Role of SUMO-1-modified PML in nuclear body formation [18].
• PIASy is the only known SUMO E3 ligase for c-Myb [19].
• These results indicate that the increased levels of SUMO-1 participate in the modulation of HIF-1alpha function through sumoylation in brain and heart [1].

Analytical, diagnostic and therapeutic context of Sumo1

• Cell culture studies indicate that both the full length and the splice variant are localized in the nucleus but differentially enhance SUMO ligation [20].
• Recognition that protein inhibitor of activated signal transducers and activators of transcription (STATs) (PIAS) proteins are SUMO E3 ligases raised the possibility that STATs may also be regulated by SUMO modification [21].
• Together, the results demonstrate that HDAC1 is modified by SUMO-1, and this modification can dramatically affect HDAC1 activity in a number of surrogate biological assays [22].
• Herein, cell-specific SUMO-1 was localized in freshly isolated, purified male germ cells and somatic cells of mouse and rat testes using Western analysis, high-resolution single-cell bioimaging, and in situ confocal microscopy of seminiferous tubules [12].
• The specific interaction between SUMO-1 and HIF-1alpha was additionally demonstrated with co-immunoprecipitation [1].

References