Stabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3

C Fu, K Ahmed, H Ding, X Ding, J Lan, Z Yang, Y Miao… - Oncogene, 2005 - nature.com
C Fu, K Ahmed, H Ding, X Ding, J Lan, Z Yang, Y Miao, Y Zhu, Y Shi, J Zhu, H Huang, X Yao
Oncogene, 2005nature.com
The PML gene of acute promyelocytic leukemia (APL) encodes a cell-growth and tumor
suppressor. PML localizes to discrete nuclear bodies (NBs) that are disrupted in APL cells,
resulting from a reciprocal chromosome translocation t (15; 17). Here we show that the
nuclear localization of PML is also regulated by SUMO-3, one of the three recently identified
SUMO isoforms in human cells. SUMO-3 bears similar subcellular distribution to those of
SUMO-1 and-2 in the interphase nuclear body, which is colocalized with PML protein …
Abstract
The PML gene of acute promyelocytic leukemia (APL) encodes a cell-growth and tumor suppressor. PML localizes to discrete nuclear bodies (NBs) that are disrupted in APL cells, resulting from a reciprocal chromosome translocation t (15; 17). Here we show that the nuclear localization of PML is also regulated by SUMO-3, one of the three recently identified SUMO isoforms in human cells. SUMO-3 bears similar subcellular distribution to those of SUMO-1 and-2 in the interphase nuclear body, which is colocalized with PML protein. However, both SUMO-2 and-3 are also localized to nucleoli, a region lacking SUMO-1. Immunoprecipitated PML protein bears SUMO-3 moiety in a covalently modified form, supporting the notion that PML is conjugated by SUMO-3. To determine the functional relevance of SUMO-3 conjugation on PML molecular dynamics, we suppressed SUMO-3 protein expression using a siRNA-mediated approach. Depletion of SUMO-3 markedly reduced the number of PML-containing NBa and their integrity, which is rescued by exogenous expression of SUMO-3 but not SUMO-1 or SUMO-2. The specific requirement of SUMO-3 for PML nuclear localization is validated by expression of SUMO-3 conjugation defective mutant. Moreover, we demonstrate that oligomerization of SUMO-3 is required for PML retention in the nucleus. Taken together, our studies provide first line of evidence showing that SUMO-3 is essential for PML localization and offer novel insight into the pathobiochemistry of APL.
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