Tsg101 and Alix Interact with Murine Leukemia Virus Gag and Cooperate with Nedd4 Ubiquitin Ligases during Budding

Segura-Morales, Carolina; Begon-Pescia, Christina; Chatellard-Causse, Christine; Sadoul, Rémy; Bertrand, Édouard; Basyuk, Eugénia

doi:10.1074/jbc.m413735200

Cited by 89 publications

(108 citation statements)

References 65 publications

(141 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Regulation of assembly of the Endosomal Sorting Complex Required for Transport (ESCRT) in the membrane vesicle trafficking by ubiquitination may be a major functional role of NEDD4, through interaction with CBL, EPS15, TSG101, HGS/ HRS, SCAMPs, and TNK2/ACK1. [32][33][34][35][36][37] The results in this report clearly show that NEDD4 interact with LC3 and plays an essential role in autophagy. It has been observed that the autophagic process shares the endosomal vesicle trafficking machinery.…”

Section: Discussionsupporting

confidence: 49%

“…29 NEDD4 also plays an important role in the retroviral budding process, which resembles the sorting process of MVBs, by ubiquitination of Gag polyproteins. 30,31 In mammalian cells, NEDD4 is involved in regulation of intracellular trafficking of receptor tyrosine kinases by ubiquitination of either endocytic or vesicle sorting proteins, such as CBL, EPS15, TSG101, HGS/HRS, SCAMPs, and TNK2/ACK1, [32][33][34][35][36][37] or the respective receptors. 38 Furthermore, NEDD4 interacts and ubiquitinates the tumor suppressor PTEN and facilitates its degradation, 39 suggesting that NEDD4 may function as an oncogenic protein and promote tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The E3 ubiquitin ligase NEDD4 is an LC3-interactive protein and regulates autophagy

et al. 2017

View full text Add to dashboard Cite

The MAP1LC3/LC3 family plays an essential role in autophagosomal biogenesis and transport. In this report, we show that the HECT family E3 ubiquitin ligase NEDD4 interacts with LC3 and is involved in autophagosomal biogenesis. NEDD4 binds to LC3 through a conserved WXXL LC3-binding motif in a region between the C2 and the WW2 domains. Knockdown of NEDD4 impaired starvation-or rapamycininduced activation of autophagy and autophagosomal biogenesis and caused aggregates of the LC3 puncta colocalized with endoplasmic reticulum membrane markers. Electron microscopy observed gigantic deformed mitochondria in NEDD4 knockdown cells, suggesting that NEDD4 might function in mitophagy. Furthermore, SQSTM1 is ubiquitinated by NEDD4 while LC3 functions as an activator of NEDD4 ligase activity. Taken together, our studies define an important role of NEDD4 in regulation of autophagy.

show abstract

Section: Discussionsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

The E3 ubiquitin ligase NEDD4 is an LC3-interactive protein and regulates autophagy

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The production of EIAV virions is strongly inhibited by overexpression of truncated Alix fragments (Martin-Serrano et al, 2003;Strack et al, 2003) or by silencing Alix expression by RNAi (Martin-Serrano et al, 2003). Similarly, Alix binds to a YPAL motif in the Gag protein of murine leukemia virus, the budding of which is impaired upon RNAi-mediated depletion of Alix (Segura-Morales et al, 2005). Interestingly, Alix binds a related motif, YPLTSL, in the p6 domain of Gag encoded by human immunodeficiency virus type 1 (HIV-1), but disruption of Alix function causes only a moderate defect in HIV-1 budding (Martin-Serrano et al, 2003;Strack et al, 2003).…”

Section: Enveloped Virus Buddingmentioning

confidence: 94%

The multiple personalities of Alix

Odorizzi

2006

Journal of Cell Science

159

150

View full text Add to dashboard Cite

Alix is a cytosolic protein in mammalian cells that was originally identified on the basis of its association with proapoptotic signaling. More recent evidence has established that Alix has a hand in regulating other cellular mechanisms, including endocytic membrane trafficking and cell adhesion. Although Alix appears to participate directly in these various activities, the role it plays in each process has largely been inferred from the functions of proteins with which it interacts. For example, recruitment of Alix to endosomes is mediated by its N-terminal Bro1 domain, the structure of which was recently solved for its yeast orthologue, Bro1. The diversity of Alix functions is due to its proline-rich C-terminus, which provides multiple protein-binding sites. With this blueprint in hand, we can now ask whether Alix acts simply as an adaptor that links different proteins into networks or, instead, contributes a specific function to distinct molecular machineries.

show abstract

“…Although it is currently assumed that MVBs play a central role in retrovirus budding, it remains uncertain whether and how components of other endosomal vesicles, including early endosomes, contribute to retroviral budding. It is reported that HLTV-1 Gag polyproteins interact first with Nedd4.1 at the plasma membrane and then with Tsg101 in late endosomes/MVB, suggesting a successive assembly and budding process through the endocytic pathway (17,18). However, neither early nor late endosomes are optimally evolved for viral assembly and release.…”

Section: Equine Infectious Anemia Virus (Eiav)mentioning

confidence: 99%

Functions of Early (AP-2) and Late (AIP1/ALIX) Endocytic Proteins in Equine Infectious Anemia Virus Budding

Chen

Vincent

Jin

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

The proline-rich L domains of human immunodeficiency virus 1 (HIV-1) and other retroviruses interact with late endocytic proteins during virion assembly and budding. In contrast, the YPDL L domain of equine infectious anemia virus (EIAV) is apparently unique in its reported ability to interact both with the 2 subunit of the AP-2 adaptor protein complex and with ALG-2-interacting protein 1 (AIP1/Alix) protein factors involved in early and late endosome formation, respectively. To define further the mechanisms by which EIAV adapts vesicle trafficking machinery to facilitate virion production, we have examined the specificity of EIAV p9 binding to endocytic factors and the effects on virion production of alterations in early and late endocytic protein expression. The results of these studies demonstrated that (i) an ϳ300-residue region of AIP1/Alix-(409 -715) was sufficient for binding to the EIAV YPDL motif; (ii) overexpression of AIP1/Alix or AP-2 2 subunit specifically inhibited YPDL-mediated EIAV budding; (iii) virion budding from a replication-competent EIAV variant with its L domain replaced by the HIV PTAP sequence was inhibited by wild type or mutant 2 to a level similar to that observed when a dominant-negative mutant of Tsg101 was expressed; and (iv) overexpression or siRNA silencing of AIP1/Alix and AP-2 revealed additive suppression of YPDL-mediated EIAV budding. Taken together, these results indicated that both early and late endocytic proteins facilitate EIAV production mediated by either YPDL or PTAP L domains, suggesting a comprehensive involvement of endocytic factors in retroviral assembly and budding that can be accessed by distinct L domain specificities. Equine infectious anemia virus (EIAV)2 is a member of the lentivirus subfamily of retroviruses, which also includes human immunodeficiency virus 1 (HIV-1). The EIAV genome is the simplest among the lentivirus family and encodes three major structural proteins (Gag, Pol, and Env) along with three accessory gene products (Tat, Rev, S2). Like all retroviruses, EIAV Gag protein is synthesized as a polyprotein that upon virion maturation is processed by virus-encoded protease to yield four major structural proteins: matrix, capsid, nucleocapsid, and p9 protein. All four structural proteins of Gag polyprotein play critical and distinctive roles in retrovirus assembly and budding. Matrix proteins direct targeting of Gag polyproteins to cell membranes for viral assembly and budding (1, 2). Both capsid and nucleocapsid have been shown to mediate Gag-Gag interactions during viral assembly, with capsid responsible for the dimerization of homologous Gag polyproteins (3, 4) and nucleocapsid essential for multimerization of Gag molecules (5, 6). The EIAV p9 protein contains a YPDL late (L) domain that is critical for virion release during the late stage of virus budding. Proline-rich L domains such as PTAP and PPPY with similar functions have also been identified from HIV-1, Rous sarcoma virus, and a variety of other enveloped viruses (7).L domains appear to...

show abstract

Tsg101 and Alix Interact with Murine Leukemia Virus Gag and Cooperate with Nedd4 Ubiquitin Ligases during Budding

Cited by 89 publications

References 65 publications

The E3 ubiquitin ligase NEDD4 is an LC3-interactive protein and regulates autophagy

The E3 ubiquitin ligase NEDD4 is an LC3-interactive protein and regulates autophagy

The multiple personalities of Alix

Functions of Early (AP-2) and Late (AIP1/ALIX) Endocytic Proteins in Equine Infectious Anemia Virus Budding

Contact Info

Product

Resources

About