HUWE1 ubiquitinates MyoD and targets it for proteasomal degradation

The Ubiquitin-conjugating Enzyme (E2) Ube2w Ubiquitinates the N Terminus of Substrates

“…The enzymes responsible for N-terminal modification have remained elusive. One E3, HUWE1 (HECT, UBA, and WWE domain-containing 1), has been shown to ubiquitinate lysineless MyoD on its N terminus, but this activity may not be physiologically relevant as HUWE1 preferentially modifies lysines and fails to modify the N terminus of wild-type MyoD (26). By contrast, eliminating all lysines in ataxin-3 does not alter the rate or extent of ubiquitination of ataxin-3 by Ube2w, strongly suggesting that the physiological target of Ube2w is the N terminus of substrates.…”

“…One HECT type E3 has been demonstrated to N-terminally ubiquitinate substrate (26), but to date no N terminus-ubiquitinating E2s have been identified, thus far excluding RING/U-box type E3s from facilitating N-terminal modification. To determine where Ube2w ubiquitinates its substrates, we monoubiquitinated several substrates with Ube2w and subjected them to mass spec analysis.…”

The Myogenic Regulatory Factors: Critical Determinants of Muscle Identity in Development, Growth and Regeneration

“…MyoD is regulated by ubiquitination at its N terminal which targets it for degradation [107,108]. MyoD is also negatively regulated by methylation which impairs its ability to induce differentiation [109].…”

Mule/Huwe1/Arf-BP1 suppresses Ras-driven tumorigenesis by preventing c-Myc/Miz1-mediated down-regulation of p21 and p15

“…Various Mule substrates are involved in apoptosis (Mcl-1) (Zhong et al 2005), DNA replication, DNA damage responses, DNA repair (TopBP1, Cdc6, and DNA polymerases b and l) (Hall et al 2007;Herold et al 2008;Parsons et al 2009;Markkanen et al 2012), and transcriptional regulation (p53, c-Myc, N-Myc, Miz1, HDAC2, and MyoD) (Adhikary et al 2005;Chen et al 2005;Zhao et al 2008;Yang et al 2010;Zhang et al 2011;Noy et al 2012). Mule attaches Lys 48 (K48)-linked polyubiquitin chains to most of its substrates, promoting their proteasomal degradation.…”