Ross Sarah, Best Jennifer L, Zon Leonard I, Gill Grace
Department of Pathology, Harvard Medical School, Children's Hospital, Boston, MA 02115, USA.
Mol Cell. 2002 Oct;10(4):831-42. doi: 10.1016/s1097-2765(02)00682-2.
The GC box binding transcription factor Sp3 both activates and represses transcription. We have found that Sp3 activity is regulated by SUMO-1 modification. Endogenous Sp3 is sumoylated and localized to the nuclear periphery and in nuclear dots. Removal of SUMO-1 from Sp3 by mutation of the SUMO acceptor lysines or expression of the SUMO-1 protease SuPr-1 converted Sp3 to a strong activator with a diffuse nuclear localization. Covalent attachment of SUMO-1 to Sp3 by gene fusion was sufficient to repress Sp3-dependent transcription and relocalize Sp3 to the nuclear periphery and nuclear dots. These studies reveal a direct effect of SUMO-1 modification on activity of a dual function transcription factor and provide a mechanism for functional specificity within the Sp transcription factor family.
GC盒结合转录因子Sp3既能激活转录，也能抑制转录。我们发现Sp3的活性受SUMO-1修饰调控。内源性Sp3被SUMO化，并定位于核周边和核点。通过SUMO受体赖氨酸突变或SUMO-1蛋白酶SuPr-1的表达从Sp3上去除SUMO-1，可将Sp3转化为具有弥散核定位的强激活剂。通过基因融合将SUMO-1共价连接到Sp3上足以抑制Sp3依赖的转录，并使Sp3重新定位于核周边和核点。这些研究揭示了SUMO-1修饰对双功能转录因子活性的直接影响，并为Sp转录因子家族内的功能特异性提供了一种机制。
