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BH3‐ligand regulates access of MCL‐1 to its E3 ligase
Author(s) -
Warr Matthew R.,
Acoca Stephane,
Liu Zhiqian,
Germain Marc,
Watson Mark,
Blanchette Mathieu,
Wing Simon S.,
Shore Gordon C.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.09.028
Subject(s) - ubiquitin ligase , hela , chemistry , ligand (biochemistry) , ubiquitin , microbiology and biotechnology , in vitro , histone , proteasome , biology , biochemistry , receptor , dna , gene
A genome wide search for new BH3‐containing Bcl‐2 family members was conducted using position weight matrices (PWM) and identified a large (480 kDa), novel BH3‐only protein, originally called LASU1 (now also known as Ureb‐1, E3 histone , ARF‐BP1, and Mule). We demonstrated that LASU1 is an E3 ligase that ubiquitinated Mcl‐1 in vitro and was required for its proteasome‐dependent degradation in HeLa cells. Of note, the BH3 domain of LASU1 interacted with Mcl‐1 but not with Bcl‐2 or Bcl‐Xl. A competing BH3‐ligand derived from Bim interacted with Mcl‐1 and prevented its interaction with LASU1 in HeLa cells, causing elevation of the steady‐state levels of Mcl‐1. This suggests that the unliganded form of Mcl‐1 is sensitive to LASU1‐mediated degradation of Mcl‐1.