The Proteasome in Terminal Plasma Cell Differentiation

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The ability of eukaryotic cells to adapt to changing environmental conditions, respond to stimuli, and differentiate relies on their capacity to control the concentration, conformation, localization, and interaction of proteins, thereby reshaping their proteome. Protein degradation plays a critical role in maintaining protein homeostasis, and hence is carefully regulated. During the spectacular and demanding metamorphosis of activated B lymphocytes, expression programs are launched in coordinated waves, and adaptive strategies are deployed to prepare for antibody secretion. Surprisingly, though, despite increased demand for proteolysis, proteasome capacity collapses. As a result, antibody-secreting cells show symptoms of proteotoxic stress, and become extremely vulnerable to proteasome inhibition. The emerging concept that proteostenosis naturally follows B-cell activation has biological and immune implications, for it provides a model to dissect the integrated regulation of protein homeostasis, and a molecular counter limiting antibody responses, of use against autoimmune diseases. Mounting evidence linking proteotoxicity with proteasome vulnerability in malignant plasma cells visualizes strategies to understand responsiveness and obviate resistance to proteasome inhibition, with implications for the biology and therapy of plasma cell dyscrasias, namely, light chain amyloidosis and multiple myeloma.

Original languageEnglish
Pages (from-to)215-222
Number of pages8
JournalSeminars in Hematology
Volume49
Issue number3
DOIs
Publication statusPublished - Jul 2012

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Proteasome Endopeptidase Complex
Plasma Cells
Cell Differentiation
Proteolysis
Homeostasis
B-Lymphocytes
Antibody-Producing Cells
Paraproteinemias
Proteins
Eukaryotic Cells
Amyloidosis
Proteome
Multiple Myeloma
Autoimmune Diseases
Antibody Formation
Light
Antibodies
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

The Proteasome in Terminal Plasma Cell Differentiation. / Cenci, Simone.

In: Seminars in Hematology, Vol. 49, No. 3, 07.2012, p. 215-222.

Research output: Contribution to journalArticle

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