Annexin A4 interacts with the NF-kappaB p50 subunit and modulates NF-kappaB transcriptional activity in a Ca2+-dependent manner.
Previously, we identified annexin A4 (ANXA4) as a candidate substrate of caspase-3. Proteomic studies were performed to identify interacting proteins with a view to determining the roles of ANXA4. ANXA4 was found to interact with the p105. Subsequent studies revealed that ANXA4 interacts with NF-kappaB through the Rel homology domain of p50. Furthermore, the interaction is markedly increased by elevated Ca(2+) levels. NF-kappaB transcriptional activity assays demonstrated that ANXA4 suppresses NF-kappaB transcriptional activity in the resting state. Following treatment with TNF-alpha or PMA, ANXA4 also suppressed NF-kappaB transcriptional activity, which was upregulated significantly early after etoposide treatment. This difference may be due to the intracellular Ca(2+) level. Additionally, ANXA4 translocates to the nucleus together with p50, and imparts greater resistance to apoptotic stimulation by etoposide. Our results collectively indicate that ANXA4 differentially modulates the NF-kappaB signaling pathway, depending on its interactions with p50 and the intracellular Ca(2+) ion level.
Jeon
Young-Joo
YJ
Medical Proteomics Research Center, KRIBB, Daejeon, 305-806, Republic of Korea.
Kim
Do-Hyung
DH
Jung
Hyeyun
H
Chung
Sang J
SJ
Chi
Seung-Wook
SW
Cho
Sayeon
S
Lee
Sang Chul
SC
Park
Byoung Chul
BC
Park
Sung Goo
SG
Bae
Kwang-Hee
KH
D017314:Annexin A4 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D052002:NF-kappa B p50 Subunit / Q000032:analysis / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017314:Annexin A4; D052002:NF-kappa B p50 Subunit; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium