Roles of sumoylation of a reptin chromatin-remodelling complex in cancer metastasis.
Defining the functional modules within transcriptional regulatory factors that govern switching between repression and activation events is a central issue in biology. Recently, we have reported the dynamic role of a beta-catenin-reptin chromatin remodelling complex in regulating a metastasis suppressor gene KAI1 (ref.1), which is capable of inhibiting the progression of tumour metastasis. Here, we identify signalling factors that confer repressive function on reptin and hence repress the expression of KAI1. Biochemical purification of a reptin-containing complex has revealed the presence of specific desumoylating enzymes that reverse the sumoylation of reptin that underlies its function as a repressor. Desumoylation of reptin alters the repressive function of reptin and its association with HDAC1. Furthermore, the sumoylation status of reptin modulates the invasive activity of cancer cells with metastatic potential. These data clearly define a functional model and provide a novel link for SUMO modification in cancer metastasis.
Kim
Jung Hwa
JH
Department of Biological Sciences, Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, South Korea.
Choi
Hee June
HJ
Kim
Bogyou
B
Kim
Mi Hyang
MH
Lee
Ji Min
JM
Kim
Ik Soo
IS
Lee
Moon Hee
MH
Choi
Soo Joon
SJ
Kim
Keun Il
KI
Kim
Su-Il
SI
Chung
Chin Ha
CH
Baek
Sung Hee
SH
D000074183:ATPases Associated with Diverse Cellular Activities; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051861:Kangai-1 Protein / Q000235:genetics; D009362:Neoplasm Metastasis; D011485:Protein Binding; D012097:Repressor Proteins; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*
C497688:CD82 protein, human; D002352:Carrier Proteins; D002843:Chromatin; D051861:Kangai-1 Protein; D012097:Repressor Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C122079:RUVBL2 protein, human