Lysosomal integral membrane protein LGP85 (LIMP-2) is ubiquitinated at the N-terminal cytoplasmic domain

Fujimoto, Keiko; Uchida, Shotaro; Amen, Riham N.S.; Ishii, Yuji; Tanaka, Yoshitaka; Hirota, Yuko

doi:10.1016/j.bbrc.2020.01.095

Cited by 1 publication

(2 citation statements)

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“…On the other hand, like Vpu, Kaposi's sarcoma-associated herpesvirus (KSHV) also counteracts HM1.24 [ 27 ]. KSHV encodes two immunomodulatory MARCH E3 Ub ligases, K3 and K5 [ 20 ]. K5 specifically ubiquitinates a lysine residue at position 18 in the cytoplasmic domain of HM1.24 [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…PCRs were performed using Pfu DNA polymerase (Toyobo, Osaka, Japan) or YieldAce DNA polymerase (Stratagene, La Jolla, CA, USA) according to manufacturer's instructions. The component parts of each chimeric DNA were joined by the splicing of overlap extension (SOE) method, as previously described [ 20 ]. All deletion mutants of HM1.24 were also constructed by SOE method, as previously described [ 10 ].…”

Section: Methodsmentioning

confidence: 99%

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HM1.24/BST-2 is constitutively poly-ubiquitinated at the N-terminal amino acid in the cytoplasmic domain

Fujimoto

Nakashima

Uchida

et al. 2020

Biochemistry and Biophysics Reports

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HM1.24 (also known as BST-2, CD317, and Tetherin) is a type II single-pass transmembrane glycoprotein, which traverses membranes using an N-terminal transmembrane helix and is anchored in membrane lipid rafts via a C-terminal glycosylphosphatidylinositol (GPI). HM1.24 plays a role in diverse cellular functions, including cell signaling, immune modulation, and malignancy. In addition, it also functions as an interferon-induced cellular antiviral restriction factor that inhibits the replication and release of diverse enveloped viruses, and which is counteracted by Vpu, an HIV-1 accessory protein. Vpu induces down-regulation and ubiquitin conjugation to the cytoplasmic domain of HM1.24. However, evidence for ubiquitination site(s) of HM1.24 remains controversial. We demonstrated that HM1.24 is constitutively poly-ubiquitinated at the N-terminal cytoplasmic domain, and that the mutation of all potential ubiquitination sites, including serine, threonine, cysteine, and lysine in the cytoplasmic domain of HM1.24, does not affect the ubiquitination of HM1.24. We further demonstrated that although a GPI anchor is necessary and sufficient for HM1.24 antiviral activities and virion-trapping, the deleted mutant of GPI does not influence the ubiquitination of HM1.24. These results suggest that the lipid raft localization of HM1.24 is not a prerequisite for the ubiquitination. Collectively, our findings demonstrate that the ubiquitination of HM1.24 occurs at the N-terminal amino acid in the cytoplasmic domain and indicate that the constitutive ubiquitination machinery of HM1.24 may differ from the Vpu-induced machinery.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%