ArticleMolecular and cellular biology2014
The E3 ligase CHIP mediates ubiquitination and degradation of mixed-lineage kinase 3.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- Protein homeostasis in the aged and diseased heart.The journal of cardiovascular aging · 2023Article
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- Mechanisms underlying melanoma invasion as a consequence of MLK3 loss.Experimental cell research · 2022Article
- The role of cell division control protein 42 in tumor and non-tumor diseases: A systematic review.Journal of Cancer · 2022Review
- LATS1 Regulates Mixed-Lineage Kinase 3 (MLK3) Subcellular Localization and MLK3-Mediated Invasion in Ovarian Epithelial Cells.Molecular and cellular biology · 2021Article
- C-terminus of Hsp70 Interacting Protein (CHIP) and Neurodegeneration: Lessons from the Bench and Bedside.Current neuropharmacology · 2021Review
- Feedback inhibition of cAMP effector signaling by a chaperone-assisted ubiquitin system.Nature communications · 2019Article
- MKK7, the essential regulator of JNK signaling involved in cancer cell survival: a newly emerging anticancer therapeutic target.Therapeutic advances in medical oncology · 2019Review
- UBXN2A enhances CHIP-mediated proteasomal degradation of oncoprotein mortalin-2 in cancer cells.Molecular oncology · 2018Article
- Regulating Cdc42 and Its Signaling Pathways in Cancer: Small Molecules and MicroRNA as New Treatment Candidates.Molecules (Basel, Switzerland) · 2018Review
- MLK3 phosphorylation by ERK1/2 is required for oxidative stress-induced invasion of colorectal cancer cells.Oncogene · 2018Article
- Osmotic and heat stress-dependent regulation of MLK4β and MLK3 by the CHIP E3 ligase in ovarian cancer cells.Cellular signalling · 2017Article
- Crosstalk and Interplay between the Ubiquitin-Proteasome System and Autophagy.Molecules and cells · 2017Review
- MLK3 Signaling in Cancer Invasion.Cancers · 2016Review
- A Decade of Boon or Burden: What Has the CHIP Ever Done for Cellular Protein Quality Control Mechanism Implicated in Neurodegeneration and Aging?Frontiers in molecular neuroscience · 2016Review
- Carboxyl terminus of HSC70-interacting protein (CHIP) down-regulates NF-κB-inducing kinase (NIK) and suppresses NIK-induced liver injury.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mixed-lineage kinase 3 (MLK3) activates mitogen-activated protein kinase (MAPK) signaling pathways and has important functions in migration, invasion, proliferation, tumorigenesis, and apoptosis. We investigated the role of the E3 ligase carboxyl terminus of Hsc70-interacting protein (CHIP) in the regulation of MLK3 protein levels. We show that CHIP interacts with MLK3 and, together with the E2 ubiquitin-conjugating enzyme UbcH5 (UbcH5a, -b, -c, or -d), ubiquitinates MLK3 in vitro. CHIP or Hsp70 overexpression promoted endogenous MLK3 ubiquitination and induced a decline in MLK3 protein levels in cells with Hsp90 inhibition. Furthermore, CHIP overexpression caused a proteasome-dependent reduction in exogenous MLK3 protein. Geldanamycin (GA), heat shock, and osmotic shock treatments also reduced the level of MLK3 protein via a CHIP-dependent mechanism. In addition, CHIP depletion in ovarian cancer SKOV3 cells increased cell invasion, and the enhancement of invasiveness was abrogated by small interfering RNA (siRNA)-mediated knockdown of MLK3. Thus, CHIP modulates MLK3 protein levels in response to GA and stress stimuli, and CHIP-dependent regulation of MLK3 is required for suppression of SKOV3 ovarian cancer cell invasion.
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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.