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BH3-ligand regulates access of MCL-1 to its E3 ligase
- Source :
- FEBS Letters; Oct2005, Vol. 579 Issue 25, p5603-5608, 6p
- Publication Year :
- 2005
-
Abstract
- Abstract: A genome wide search for new BH3-containing Bcl-2 family members was conducted using position weight matrices (PWM) and identified a large (480kDa), novel BH3-only protein, originally called LASU1 (now also known as Ureb-1, E3<superscript>histone</superscript>, 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. [Copyright &y& Elsevier]
- Subjects :
- CLONE cells
CANCER cells
CELLULAR pathology
CELL culture
Subjects
Details
- Language :
- English
- ISSN :
- 00145793
- Volume :
- 579
- Issue :
- 25
- Database :
- Complementary Index
- Journal :
- FEBS Letters
- Publication Type :
- Academic Journal
- Accession number :
- 18781989
- Full Text :
- https://doi.org/10.1016/j.febslet.2005.09.028