Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR

Huabin Zhu, Brinda Bhatt, Sathish Sivaprakasam, Yafei Cai, Siyang Liu, Sai Karthik Kodeboyina, Nikhil Patel, Natasha Marie Savage, Ashok Kumar Sharma, Randal J. Kaufman, Honglin Li, Nagendra Singh

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Article number1084
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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Unfolded Protein Response
Plasma Cells
proteins
Plasmas
expansion
cells
Proteins
lysine
Lysine
Immunoglobulins
Reticulum
stimulation
genes
Up-Regulation
Genes
Chemical activation
activation

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR. / Zhu, Huabin; Bhatt, Brinda; Sivaprakasam, Sathish; Cai, Yafei; Liu, Siyang; Kodeboyina, Sai Karthik; Patel, Nikhil; Savage, Natasha Marie; Sharma, Ashok Kumar; Kaufman, Randal J.; Li, Honglin; Singh, Nagendra.

In: Nature Communications, Vol. 10, No. 1, 1084, 01.12.2019.

Research output: Contribution to journalArticle

Zhu, Huabin ; Bhatt, Brinda ; Sivaprakasam, Sathish ; Cai, Yafei ; Liu, Siyang ; Kodeboyina, Sai Karthik ; Patel, Nikhil ; Savage, Natasha Marie ; Sharma, Ashok Kumar ; Kaufman, Randal J. ; Li, Honglin ; Singh, Nagendra. / Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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