Abstract
ANP32B belongs to a family of evolutionary conserved acidic nuclear phosphoproteins (ANP32A-H). Family members have been described as multifunctional regulatory proteins and proto-oncogenic factors affecting embryonic development, cell proliferation, apoptosis, and gene expression at various levels. Involvement of ANP32B in multiple processes of cellular life is reflected by the previous finding that systemic gene knockout (KO) of Anp32b leads to embryonic lethality in mice. Here, we demonstrate that a conditional KO of Anp32b is well tolerated in adult animals. However, after immune activation splenocytes isolated from Anp32b KO mice showed a strong commitment towards Th17 immune responses. Therefore, we further analyzed the respective animals in vivo using an experimental autoimmune encephalomyelitis (EAE) model. Interestingly, an exacerbated clinical score was observed in the Anp32b KO mice. This was accompanied by the finding that animal-derived T lymphocytes were in a more activated state, and RNA sequencing analyses revealed hyperactivation of several T lymphocyte-associated immune modulatory pathways, attended by significant upregulation of Tfh cell numbers that altogether might explain the observed strong autoreactive processes. Therefore, Anp32b appears to fulfill a role in regulating adequate adaptive immune responses and, hence, may be involved in dysregulation of pathways leading to autoimmune disorders and/or immune deficiencies.
Highlights
ANP32 proteins belong to a relatively new protein family of evolutionary conserved acidic nuclear phosphoproteins (ANP32A-H)
The floxed Anp32b allele was bred to homozygosity (Fig. S2a) and the tamoxifen induced Anp32b KO was established at the chromosomal and transcriptome level in several organs and tissues (Figs S2b,c and S3)
Several in vitro studies demonstrated the involvement of the acidic protein rich in leucines ANP32B in the regulation of cell proliferation, apoptosis, cell cycle progression and gene expression at the epigenetic and posttranscriptional level[7,9,10,13,24,31,32,41]
Summary
ANP32 proteins belong to a relatively new protein family of evolutionary conserved acidic nuclear phosphoproteins (ANP32A-H). Several studies showed a high conservation of these proteins, between the individual family members, and between the various eukaryotic species[4,5,6] These studies imply that ANP32 proteins originate from one single ancestor gene. ANP32A, B and E proteins harbor classical basic nuclear localization signals (NLS) for importin-dependent nuclear import and one or two nuclear export signals (NES) for CRM1-dependent nuclear exit[7,8,9,10] These ANP32 family members are expressed at varying levels in several tissues and cell types. Further investigations identified ANP32B as a negative regulator of caspase-3-dependent apoptosis, suggesting that this ANP32 family member is possibly an antagonist of ANP32A in regulating tissue homeostasis[23,32,33]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
