UBE2M Human
Description
Role in Cellular Pathways
UBE2M is indispensable in multiple cellular processes:
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Neddylation of Cullins: Facilitates the activation of CRLs (e.g., CUL1, CUL2, CUL3, CUL4A/B) by conjugating NEDD8 to their cullin subunits, enabling substrate recognition and degradation .
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DNA Damage Response: Recruits to DNA damage sites, modulating repair mechanisms and apoptosis .
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Stress Response: Transcriptionally regulated by HIF-1α and c-JUN/AP1 under hypoxia or MLN4924 treatment .
Clinical Relevance in Cancer
UBE2M is overexpressed in multiple cancers and associated with poor prognosis. Below are key findings from recent studies:
Mechanistic Insights:
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Breast Cancer: UBE2M stabilizes estrogen receptor alpha (ERα) by inhibiting its ubiquitination via CUL3/CUL4A-E6AP axis .
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HCC: UBE2M-mediated β-catenin stabilization drives cyclin D1 expression, enhancing proliferation .
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CRC: Wnt/β-catenin signaling upregulates UBE2M, promoting chemotherapy resistance .
Therapeutic Targeting of UBE2M
UBE2M inhibition has emerged as a promising strategy to counteract cancer progression:
Interactome and Regulatory Networks
UBE2M interacts with key components of the neddylation machinery and stress-response pathways:
Table 2: Key UBE2M Interactors and Functions
Experimental Models and Tools
Recombinant UBE2M is used in biochemical assays to study neddylation dynamics:
Product Specs
Product Science Overview
UBE2M plays a crucial role in the process of neddylation, which involves the conjugation of the ubiquitin-like protein Neural Precursor Cell Expressed, Developmentally Down-regulated 8 (NEDD8) to substrate proteins . This process is essential for the regulation of various cellular functions, including morphogenesis and cell cycle progression .
The neddylation pathway requires the coordinated activities of UBE2M and the APPBPI/UBA3 heterodimer, a NEDD8-activating (E1) enzyme . UBE2M receives NEDD8 from the E1 enzyme and subsequently interacts with a NEDD8 ligase (E3) to conjugate NEDD8 to target proteins . This modification modulates the levels of several key proteins, including p27/Kip1, beta-Catenin, and members of the Cullin family .
Recombinant human UBE2M is produced using Escherichia coli (E. coli) expression systems . The recombinant protein is typically supplied as a solution in HEPES, NaCl, TCEP, and Glycerol, and is shipped with dry ice to maintain stability . It is recommended to store the protein at -70°C to ensure its longevity .
