Advanced SearchSearch Tips
TCP10L synergizes with MAD1 in transcriptional suppression and cell cycle arrest through mutual interaction
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : BMB Reports
  • Volume 49, Issue 6,  2016, pp.325-330
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2016.49.6.248
 Title & Authors
TCP10L synergizes with MAD1 in transcriptional suppression and cell cycle arrest through mutual interaction
Shen, Suqin; Zuo, Jie; Feng, Huan; Bai, Meirong; Wang, Chenji; Wei, Youheng; Li, Yanhong; Le, Yichen; Wu, Jiaxue; Wu, Yanhua; Yu, Long;
  PDF(new window)
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.
Hepatocellular carcinoma;MAX dimerization protein 1;Protein degradation;Protein-protein interaction;T-complex protein 10A homolog 2;
 Cited by
Luscher B (2012) MAD1 and its life as a MYC antagonist: an update. Eur J Cell Biol 91, 506-514 crossref(new window)

Sommer A, Bousset K, Kremmer E, Austen M and Luscher B (1998) Identification and characterization of specific DNA-binding complexes containing members of the Myc/Max/Mad network of transcriptional regulators. J Biol Chem 273, 6632-6642 crossref(new window)

van Riggelen J, Yetil A and Felsher DW (2010) MYC as a regulator of ribosome biogenesis and protein synthesis. Nat Rev Cancer 10, 301-309 crossref(new window)

Cultraro CM, Bino T and Segal S (1997) Regulated expression and function of the c-Myc antagonist, Mad1, during a molecular switch from proliferation to differentiation. Curr Top Microbiol Immunol 224, 149-158

Cerni C, Skrzypek B, Popov N et al (2002) Repression of in vivo growth of Myc/Ras transformed tumor cells by Mad1. Oncogene 21, 447-459 crossref(new window)

Laherty CD, Yang WM, Sun JM, Davie JR, Seto E and Eisenman RN (1997) Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression. Cell 89, 349-356 crossref(new window)

Chen Z, Yu L, Wu H et al (2003) Identification of a novel liver-specific expressed gene, TCP10L, encoding a human leucine zipper protein with transcription inhibition activity. J Hum Genet 48, 556-563 crossref(new window)

Zhong Z, Qiu J, Chen X et al (2008) Identification of TCP10L as primate-specific gene derived via segmental duplication and homodimerization of TCP10L through the leucine zipper motif. Mol Biol Rep 35, 171-178 crossref(new window)

Zuo J, Cai H, Wu Y et al TCP10L acts as a tumor suppressor by inhibiting cell proliferation in hepatocellular carcinoma. Biochem Biophys Res Commun 446, 61-67 crossref(new window)

Jiang DJ, Yu HX, Hexige SY et al (2004) Human liver specific transcriptional factor TCP10L binds to MAD4. J Biochem Mol Biol 37, 402-407 crossref(new window)

Wang Y, Toury R, Hauchecorne M and Balmain N (1997) Expression and subcellular localization of the Myc superfamily proteins: c-Myc, Max, Mad1 and Mxi1 in the epiphyseal plate cartilage chondrocytes of growing rats. Cell Mol Biol (Noisy-le-grand) 43, 175-188

Rottmann S and Luscher B (2006) The Mad side of the Max network: antagonizing the function of Myc and more. Curr Top Microbiol Immunol 302, 63-122

Xu L, Zhu J, Hu X et al (2007) c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for Mad1. Mol Cell 28, 914-922 crossref(new window)

Yu H, Jiang D, Guo Z et al (2005) TCP10L is expressed specifically in spermatogenic cells and binds to death associated protein kinase-3. Int J Androl 28, 163-170 crossref(new window)

Kawai T, Matsumoto M, Takeda K, Sanjo H and Akira S (1998) ZIP kinase, a novel serine/threonine kinase which mediates apoptosis. Mol Cell Biol 18, 1642-1651 crossref(new window)

Komatsu S and Ikebe M (2004) ZIP kinase is responsible for the phosphorylation of myosin II and necessary for cell motility in mammalian fibroblasts. J Cell Biol 165, 243-254 crossref(new window)

Brognard J, Zhang YW, Puto LA and Hunter T (2011) Cancer-associated loss-of-function mutations implicate DAPK3 as a tumor-suppressing kinase. Cancer Res 71, 3152-3161 crossref(new window)

Hurlin PJ, Queva C, Koskinen PJ et al (1996) Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation. EMBO J 15, 2030

Xu D, Popov N, Hou M et al (2001) Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells. Proc Natl Acad Sci U S A 98, 3826-3831 crossref(new window)

Gunes C, Lichtsteiner S, Vasserot AP and Englert C (2000) Expression of the hTERT gene is regulated at the level of transcriptional initiation and repressed by Mad1. Cancer Res 60, 2116-2121

Werner S, Beer HD, Mauch C and Luscher B (2001) The Mad1 transcription factor is a novel target of activin and TGF-beta action in keratinocytes: possible role of Mad1 in wound repair and psoriasis. Oncogene 20, 7494-7504 crossref(new window)

Zhu J, Blenis J and Yuan J (2008) Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1. Proc Natl Acad Sci U S A 105, 6584-6589 crossref(new window)