• BMB Reports
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• v.49 no.6
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• pp.325-330
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• 2016

T-complex protein 10A homolog 2 (TCP10L) was previously demonstrated to be a potential tumor suppressor in human hepatocellular carcinoma (HCC). However, little is known about the molecular mechanism. MAX dimerization protein 1 (MAD1) is a key transcription suppressor that is involved in regulating cell cycle progression and Myc-mediated cell transformation. In this study, we identified MAD1 as a novel TCP10L-interacting protein. The interaction depends on the leucine zipper domain of both TCP10L and MAD1. TCP10L, but not the interaction-deficient TCP10L mutant, synergizes with MAD1 in transcriptional repression, cell cycle G1 arrest and cell growth suppression. Mechanistic exploration further revealed that TCP10L is able to stabilize intracellular MAD1 protein level. Consistently, the MAD1-interaction-deficient TCP10L mutant exerts no effect on stabilizing the MAD1 protein. Taken together, our results strongly indicate that TCP10L stabilizes MAD1 protein level through direct interaction, and they cooperatively regulate cell cycle progression.

• Journal of Life Science
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• v.30 no.1
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• pp.106-112
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• 2020

Aminoacyl tRNA synthetase complex interacting multifunctional protein 2 (AIMP2) is a scaffolding protein required for the assembly of multi-tRNA synthetase, and it can exert pro-apoptotic activity in response to DNA damage. In the presence of DNA damage, AIMP2 binds to mouse double minute 2 homolog (MDM2) to protect p53 from MDM2 attack. TGF-β signaling results in the nuclear translocation of AIMP2, whereby AIMP2 interacts with FUSE-binding protein, and, thus, suppresses c-myc. TNF receptor-associated factor 2 (TRAF2) is an important mediator between TNF-receptors 1 and 2 which are involved in the signaling of c-Jun N-terminal kinase (JNK), nuclear factor κB (NF-κB), and p38 mitogen-activated protein kinases (MAPKs). TRAF2 is required for the activations of JNK and NF-κB via TNF-α and the mediation of anti-apoptosis signaling. AIMP2 can also enhance pro-apoptosis in the TNF-α signaling. During this signaling, AIMP2 assists the association of E3 ubiquitin ligase, the cellular inhibitor of apoptosis protein 1 (c-IAP1) which is well known and responsible for the degradation of TRAF2. The formation of a complex among AIMP2, TRAF2, and c-IAP1 results in proteasome-mediated TRAF2 degradation. AIMP2 can induce apoptosis via downregulation of TRAF2 to interact directly in TNF-α signaling. This review provides new insight into the molecular mechanism responsible for AIMP2 and TRAF2 complex formation and treatments for TNFα-associated diseases.

• BMB Reports
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• v.53 no.8
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• pp.431-436
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• 2020

Alpha-fetoprotein (AFP) is one of the most commonly used and reliable biomarkers for Hepatocellular carcinoma（HCC). However, the underlying mechanism of AFP expression in HCC is poorly understood. In this study, we found that TCP10L, a gene specifically expressed in the liver, is down-regulated in HCC and that its expression inversely correlates with AFP expression. Moreover, overexpression of TCP10L suppresses AFP expression whereas knockdown of TCP10L increases AFP expression, suggesting that TCP10L might be a negative regulator of AFP. We found that TCP10L is associated with the AFP promoter and inhibits AFP promoter-driven transcriptional activity. Taken together, these results indicate that TCP10L negatively regulates AFP expression in HCC and that it could be a potential prognostic marker and therapeutic target for HCC.