The tumor suppressor annexin A10 is a novel component of nuclear paraspeckles

Abstract

Annexin A10 is the latest identified member of the annexin family of Ca(2+)- and phospholipid-binding proteins. In previous studies, downregulation of annexin A10 was correlated with dedifferentiation, invasion, and tumor progression, pointing to a possible tumor suppressor role. However, the biochemical characteristics and functions of annexin A10 remain unknown. We show that annexin A10 displays biochemical characteristics atypical for an annexin, indicating a Ca(2+)- and membrane-binding-independent function. Annexin A10 co-localizes with the mRNA-binding proteins SFPQ and PSPC1 at paraspeckles, an only recently discovered nuclear body, and decreases paraspeckle numbers when overexpressed in HeLa cells. In addition, annexin A10 relocates to dark perinucleolar caps upon transcriptional inhibition of RNA polymerase II. We mapped the cap-binding function of annexin A10 to the proximal part of the core domain, which is missing in the short isoform of annexin A10, and show its independence from the remaining functional type II Ca(2+)-binding site. In contrast to this, paraspeckle recruitment required additional core regions and was negatively affected by the mutation of the last type II Ca(2+)-binding site. Additionally, we show that overexpression of annexin A10 in HeLa cells increases their sensitivity to apoptosis and reduces colony formation. The identification of unique nuclear and biochemical characteristics of annexin A10 points towards its membrane-independent role in paraspeckle-associated mRNA regulation or processing.

Loss of maternal ANNEXIN A10 via a 34-kb deleted-type copy number variation is associated with embryonic mortality in Japanese Black cattle

“…They also play critical roles in the inhibition of coagulation and inflammation, reviewed in [32, 33]. ANXA10, is a member of the ANNEXIN gene family; however, it has only one Ca 2+ binding site [34] and displays a low capacity for phospholipids that are dependent on Ca 2+ [35]. The functions of ANXA10 in vivo, including those relevant to embryonic mortality, have not yet been evaluated.…”

Simvastatin Up-Regulates Annexin A10 That Can Inhibit the Proliferation, Migration, and Invasion in Androgen-Independent Human Prostate Cancer Cells

“…We found that the annexin‐A10 (ANXA10) gene was more strongly expressed in cells receiving statins than those not receiving statins. ANXA10 is the most recently identified member of the annexin family of calcium‐ and phospholipid‐binding proteins . In previous studies, down‐regulation of ANXA10 was correlated with dedifferentiation, invasion, and tumor progression, pointing to a possible tumor suppressor role .…”

“…ANXA10 is the most recently identified member of the annexin family of calcium‐ and phospholipid‐binding proteins . In previous studies, down‐regulation of ANXA10 was correlated with dedifferentiation, invasion, and tumor progression, pointing to a possible tumor suppressor role . However, whether ANXA10 has a specific function in prostate cancer remains unclear.…”

Structural Study on Apoptosis of Chronic Eosinophilic Leukemia Cells by Interaction of S100A8 with Splicing Factor, Proline and Glutamine-Rich

“…Paraspeckle component 1 (PSPC1), one of the three DBHS proteins, also colocalized with anxA10GFP in resting cells. This study indicated that colocalization and interaction between SFPQ and annexin 10A have an influence on the apoptosis (Quiskamp et al, 2014). Annexin 10A binding to SFPQ in the nucleus, and the overexpression of annexin 10A is reported an inducing factor for tumor cell apoptosis.…”