Hormonal
The E3 ubiquitin ligase MAFbx (Atrogin-1) directly binds to MyoD via a conserved LXXLL motif interaction, leading to MyoD ubiquitination and proteasomal degradation, which suppresses myogenic differentiation.
This research identifies MAFbx as a key enzyme that degrades MyoD, a master regulator of muscle growth. High levels of MAFbx, often seen during muscle atrophy (caused by fasting, aging, or disuse), lead to the loss of MyoD and inhibit muscle formation. Preserving muscle mass may involve mechanisms that regulate or inhibit MAFbx activity.
Here we report that MyoD interacts with Atrogin-1/MAFbx (MAFbx), a striated muscle-specific E3 ubiquitin ligase dramatically up-regulated in atrophying muscle. A core LXXLL motif sequence in MyoD is necessary for binding to MAFbx... Overexpression of MAFbx suppresses MyoD-induced differentiation and inhibits myotube formation.
Why this rating
High-quality biochemical evidence (yeast two-hybrid, co-IP, in vitro ubiquitination, in vivo models) with clear mechanistic validation via mutations.
Source
Degradation of MyoD Mediated by the SCF (MAFbx) Ubiquitin Ligase
Lionel Tintignac et al. · Journal of Biological Chemistry · 2004
DOI 10.1074/jbc.m411346200
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →