title: TCP10L synergizes with MAD1 in transcriptional suppression and cell cycle arrest through mutual interaction.
abstract: 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. [BMB Reports 2016; 49(6): 325-330].
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Suqin
authors.initials: S
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zuo
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Feng
authors.affiliation: Cardiovascular Research Institute and Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Meirong
authors.initials: M
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Chenji
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Youheng
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Yichen
authors.initials: Y
authors.lastname: Le
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Jiaxue
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D016350:Leucine Zippers; D011485:Protein Binding; D000072417:Protein Domains; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D059748:Proteolysis; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C079439:MXD1 protein, human; D011506:Proteins; D012097:Repressor Proteins; C533392:TCP10L3 protein, human