ArticleThe Journal of biological chemistry2011
Mitochondrion-dependent N-terminal processing of outer membrane Mcl-1 protein removes an essential Mule/Lasu1 protein-binding site.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- The E3 ubiquitin ligase HUWE1 is required for KRAS-induced lung cancer.Cell death & disease · 2026Article
- MCL1 may not mediate chemoresistance.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms of MCL-1 Protein Stability Induced by MCL-1 Antagonists in B-Cell Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Increased MCL-1 synthesis promotes irradiation-induced nasopharyngeal carcinoma radioresistance via regulation of the ROS/AKT loop.Cell death & disease · 2022Article
- The role of Ubiquitination in Apoptosis and Necroptosis.Cell death and differentiation · 2022Review
- The multiple mechanisms of MCL1 in the regulation of cell fate.Communications biology · 2021Review
- Fibroblast growth factor receptor inhibition induces loss of matrix MCL1 and necrosis in cholangiocarcinoma.Journal of hepatology · 2018Article
- Delineating Crosstalk Mechanisms of the Ubiquitin Proteasome System That Regulate Apoptosis.Frontiers in cell and developmental biology · 2018Review
- Structure-Function Analysis of the Mcl-1 Protein Identifies a Novel Senescence-regulating Domain.The Journal of biological chemistry · 2015Article
- Maritoclax and dinaciclib inhibit MCL-1 activity and induce apoptosis in both a MCL-1-dependent and -independent manner.Oncotarget · 2015Article
- Regulation of mitochondrial nutrient and energy metabolism by BCL-2 family proteins.Trends in endocrinology and metabolism: TEM · 2015Review
- Dichotomous role of pancreatic HUWE1/MULE/ARF-BP1 in modulating beta cell apoptosis in mice under physiological and genotoxic conditions.Diabetologia · 2014Article
- Article
- Programming cancer cells for high expression levels of Mcl1.EMBO reports · 2013Review
- Multiple functions of BCL-2 family proteins.Cold Spring Harbor perspectives in biology · 2013Review
- Delving deeper: MCL-1's contributions to normal and cancer biology.Trends in cell biology · 2013Review
- Multipolar functions of BCL-2 proteins link energetics to apoptosis.Trends in cell biology · 2012Review
- Mcl-1 rescues a glitch in the matrix.Nature cell biology · 2012Article
- Selectively targeting Mcl-1 for the treatment of acute myelogenous leukemia and solid tumors.Genes & development · 2012Article
- Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin.Developmental cell · 2012Article
Corrections and comments
- Commented on by
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Mcl-1, a pro-survival member of the Bcl-2 family located at the mitochondrial outer membrane, is subject to constitutive ubiquitylation by the Bcl-2 homology 3-only E3 ligase, Mule/Lasu1, resulting in rapid steady-state degradation via the proteasome. Insertion of newly synthesized Mcl-1 into the mitochondrial outer membrane is dependent on its C-terminal transmembrane segment, but once inserted, the N terminus of a portion of the Mcl-1 molecules can be subject to proteolytic processing. Remarkably, this processing requires an intact electrochemical potential across the inner membrane. Three lines of evidence directed at the endogenous protein, however, indicate that the resulting Mcl-1ΔN isoform resides in the outer membrane: (i) full-length Mcl-1 and Mcl-1ΔN resist extraction by alkali but are accessible to exogenous protease; (ii) almost the entire populations of Mcl-1 and Mcl-1ΔN are accessible to the membrane-impermeant Cys-reactive agent 4-acetamido-4'-[(iodoacetyl)amino]stilbene-2,2'-disulfonic acid; and (iii) Mcl-1 and Mcl-1ΔN exhibit equivalent chemical cross-linking to Bak in intact mitochondria, an Mcl-1 binding partner located in the outer membrane. In addition to the Mule Bcl-2 homology 3 domain, we show that interaction between Mcl-1 and Mule also requires the extreme N terminus of Mcl-1, which is lacking in Mcl-1ΔN. Thus, Mcl-1ΔN does not interact with Mule, exhibits reduced steady-state ubiquitylation, evades the hyper-rapid steady-state degradation that is observed for full-length Mcl-1 in response to treatments that limit global protein synthesis, and confers resistance to UV stress-induced cell death.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.