Ufbp1 Promotes Plasma Cell Development and ER Expansion by Modulating Distinct Branches of UPR

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Mar 8

PMID 30842412

Citations 51

Authors

Huabin Zhu

Brinda Bhatt

Sathish Sivaprakasam

Yafei Cai

Siyang Liu

Sai Karthik Kodeboyina

Nikhil Patel

Natasha M Savage

Ashok Sharma

Randal J Kaufman

Honglin Li

Nagendra Singh

Affiliations

Soon will be listed here.

Abstract

The IRE1α/XBP1 branch of unfolded protein response (UPR) pathway has a critical function in endoplasmic reticulum (ER) expansion in plasma cells via unknown mechanisms; interestingly, another UPR branch, PERK, is suppressed during plasma cell development. Here we show that Ufbp1, a target and cofactor of the ufmylation pathway, promotes plasma cell development by suppressing the activation of PERK. By contrast, the IRE1α/XBP1 axis upregulates the expression of Ufbp1 and ufmylation pathway genes in plasma cells, while Ufbp1 deficiency impairs ER expansion in plasma cells and retards immunoglobulin production. Structure and function analysis suggests that lysine 267 of Ufbp1, the main lysine in Ufbp1 that undergoes ufmylation, is dispensable for the development of plasmablasts, but is required for immunoglobulin production and stimulation of ER expansion in IRE1α-deficient plasmablasts. Thus, Ufbp1 distinctly regulates different branches of UPR pathway to promote plasma cell development and function.

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