Ubiquitin-conjugating enzyme E2 D1 (Ube2D1) mediates lysine-independent ubiquitination of the E3 ubiquitin ligase March-I

Lei, Lei; Bandola-Simon, Joanna; Roche, Paul A.

doi:10.1074/jbc.ra117.001322

Cited by 28 publications

(24 citation statements)

References 31 publications

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“…The five most central members of the Cluster 1 network (based on betweenness centrality) were SQSTM1 , UBE2D1 , CBL , TRIM21 , and HIF1A ( Supplementary Table 3 ). SQSTM1 is involved in multiple protein degradation pathways, UBE2D1 is a ubiquitin-conjugating enzyme, and CBL and TRIM21 are both ubiquitin ligases – although all four are likely to play an important role in the response to ROS, and SQSTM1 is a well-characterized NRF2 target gene, the network centrality of these proteins can be explained by the broad protein-protein interaction spectrum associated with ubiquitin mediated degradation [41] , [42] , [43] , [44] . However, HIF1A , which encodes HIF1α, is typically associated with hypoxic stress and, therefore, an unanticipated member of this gene set.…”

Section: Resultsmentioning

confidence: 99%

Identification of a functional antioxidant response element at the HIF1A locus

et al. 2018

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Reactive oxygen species (ROS), which are a byproduct of oxidative metabolism, serve as signaling molecules in a number of physiological settings. However, if their levels are not tightly maintained, excess ROS lead to potentially cytotoxic oxidative stress. Accordingly, several transcriptional regulatory networks have evolved to include components that are highly ROS-responsive. Depending on the context, these regulatory networks can leverage ROS to respond to nutrient conditions, metabolism, or other physiological signals, or to respond to oxidative stress. However, ROS signaling is complex, so regulatory interactions between various ROS-responsive transcription factors are still being mapped out. Here we show that the transcription factor NRF2, a key regulator of the adaptive response to oxidative stress, directly regulates expression of HIF1A, which encodes HIF1α, a key transcriptional regulator of the adaptive response to hypoxia. We used an integrative genomics approach to identify HIF1A as a ROS-responsive transcript and we found an NRF2-bound antioxidant response element (ARE) approximately 30 kilobases upstream of HIF1A. This ARE sequence is deeply conserved, and we verified that it is directly bound and activated by NRF2. In addition, we found that HIF1A is upregulated in breast and bladder tumors with high NRF2 activity. Taken together, our results demonstrate that NRF2 targets a functional ARE at the HIF1A locus, and reveal a direct regulatory connection between two important oxygen responsive transcription factors.

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Section: Resultsmentioning

confidence: 99%

Identification of a functional antioxidant response element at the HIF1A locus

et al. 2018

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“…shRNA knockdown of the E2 Ube2D1 strongly stabilized wild-type MARCH1; however, whether this also applies to lysine-free MARCH1 was not addressed. While the responsible E3 ligase(s) has not yet been identified, it appears that MARCH1 itself is not responsible, or is at least not required, as mutation of catalytic residues to disable its E3 activity did not prevent its ubiquitination [46].…”

Section: Non-lysine Ubiquitination Targets a Variety Of Cellular Procmentioning

confidence: 99%

Cellular functions and molecular mechanisms of non-lysine ubiquitination

2019

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Protein ubiquitination is of great cellular importance through its central role in processes such as degradation, DNA repair, endocytosis and inflammation. Canonical ubiquitination takes place on lysine residues, but in the past 15 years non-lysine ubiquitination on serine, threonine and cysteine has been firmly established. With the emerging importance of non-lysine ubiquitination, it is crucial to identify the responsible molecular machinery and understand the mechanistic basis for non-lysine ubiquitination. Here, we first provide an overview of the literature that has documented non-lysine ubiquitination. Informed by these examples, we then discuss the molecular mechanisms and cellular implications of non-lysine ubiquitination, and conclude by outlining open questions and future perspectives in the field.

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“…For examples, MARCH1 keeps a low protein level in antigen presentation cells (APCs) of human and mice by its TM-mediated dimerization, leading to autoubiquitination and degradation (57). However, it has been demonstrated that both wild-type and catalytically inactive MARCH1 are ubiquitinated in HeLa cells, suggesting that MARCH1 can be ubiquitinated by as yet unidentified E3 ligases (58). The stability of MARCH5-8, and 10 is tightly regulated by their RING-CH finger-mediated atutoubiquitination (4, 12, 15, 18, 27, 29).…”

Section: Properties Of the March E3 Ligase Family Membersmentioning

confidence: 99%

The Membrane-Associated MARCH E3 Ligase Family: Emerging Roles in Immune Regulation

Lin

Shu

2019

Front. Immunol.

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The membrane-associated RING-CH-type finger (MARCH) proteins of E3 ubiquitin ligases have emerged as critical regulators of immune responses. MARCH proteins target immune receptors, viral proteins as well as components in innate immune response for polyubiquitination and degradations via distinct routes. This review summarizes the current progress about MARCH proteins and their regulation on immune responses.

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Ubiquitin-conjugating enzyme E2 D1 (Ube2D1) mediates lysine-independent ubiquitination of the E3 ubiquitin ligase March-I

Abstract: March

Cited by 28 publications

References 31 publications

Identification of a functional antioxidant response element at the HIF1A locus

Identification of a functional antioxidant response element at the HIF1A locus

Cellular functions and molecular mechanisms of non-lysine ubiquitination

The Membrane-Associated MARCH E3 Ligase Family: Emerging Roles in Immune Regulation

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