Gene Regulation In Ageing and Age-Related Diseases

Currently, the Calkhoven lab studies a specific pathway (mTORC1-pathway) that senses if enough nutrients and energy are available to regulate cell growth, through the control of protein synthesis and/or other metabolic processes. The Calkhoven lab are particular interested in the function of mRNA control elements, protein factors and microRNAs that are involved in mTORC1-controlled processes. Using mouse models they examine the function of these elements, and other factors, on organismal health and life span determination. In addition, they study the modification of gene-regulatory proteins by cellular metabolites and how this regulates cell function under different nutrition conditions. With the aim of ‘translating’ the fundamental research into clinical-pharmacological applications, the lab is also involved in developing reporter-systems for potential compound screening strategies.

• Zidek LM, Ackermann T, Hartleben G, Eichwald S, Kortman G, Kiehntopf M, Leutz A, Sonenberg N, Wang Z-Q, von Maltzahn J, Müller C, and Calkhoven CF. (2015) Deficiency in mTORC1-controlled C/EBPβ-mRNA translation improves metabolic health in mice. EMBO Rep.
  • View abstract
  • View PDF
• Min W, Bruhn C, Grigaravicius P, Zhou ZW, Li F, Krüger A, Siddeek B, Greulich KO, Popp O, Meisezahl C, Calkhoven CF, Bürkle A, Xu X, Wang ZQ. (2015) Poly(ADP-ribose) binding to Chk1 at stalled replication forks is required for S-phase checkpoint activation. Nature Communications.
  • View abstract
  • View PDF
• Dey S, Savant S, Teske BF, Hatzoglou M, Calkhoven CF, Wek RC. (2012) Transcriptional repression of ATF4 gene by CCAAT/enhancer-binding protein β (C/EBPβ) differentially regulates integrated stress response. The journal of biological chemistry.
  • View abstract
  • View PDF
• Mielke N, Schwarzer R, Calkhoven CF, Kaufman RJ, Dörken B, Leutz A, Jundt F. (2011) Eukaryotic initiation factor 2alpha phosphorylation is required for B-cell maturation and function in mice. Haematologica.
  • View abstract
  • View PDF
• Luther J, Driessler F, Megges M, Hess A, Herbort B, Mandic V, Zaiss MM, Reichardt A, Zech C, Tuckermann JP, Calkhoven CF, Wagner EF, Schett G, David JP. (2011) Elevated Fra-1 expression causes severe lipodystrophy. Journal of cell science.
  • View abstract
  • View PDF
• Juenemann K, Weisse C, Reichmann D, Kaether C, Calkhoven CF, Schilling G. (2010) Modulation of mutant huntingtin N-terminal cleavage and its effect on aggregation and cell death. Neurotoxicity research
  • View abstract
  • View PDF
• Müller C, Calkhoven CF. (2010) C/EBPα enters the nucleolus. Cell Cycle
  • View abstract
  • View PDF
• Müller C, Bremer A, Schreiber S, Eichwald S, Calkhoven CF. (2010) Nucleolar retention of a translational C/EBPalpha isoform stimulates rDNA transcription and cell size. The EMBO Journal.
  • View abstract
  • View PDF
• Wethmar K, Bégay V, Smink JJ, Zaragoza K, Wiesenthal V, Dörken B, Calkhoven CF, Leutz A. (2010) C/EBPbetaDeltauORF mice--a genetic model for uORF-mediated translational control in mammals. Genes & Development.
  • View abstract
  • View PDF
• van Gorp AG, van der Vos KE, Brenkman AB, Bremer A, van den Broek N, Zwartkruis F, Hershey JW, Burgering BM, Calkhoven CF, Coffer PJ. (2008) AGC kinases regulate phosphorylation and activation of eukaryotic translation initiation factor 4B. Oncogene.
  • View abstract
  • View PDF
• Wiesenthal V, Leutz A, Calkhoven CF. (2006) Analysis of translation initiation using a translation control reporter system. Nature Protocols.
  • View abstract
  • View PDF
• Wiesenthal V, Leutz A, Calkhoven CF. (2006) A translation control reporter system (TCRS) for the analysis of translationally controlled processes in the vertebrate cell. Nucleic Acids Research.
  • View abstract
  • View PDF
• Jundt F, Raetzel N, Müller C, Calkhoven CF, Kley K, Mathas S, Lietz A, Leutz A, Dörken B. (2005) A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein {beta} and NF-{kappa}B activity in Hodgkin and anaplastic large cell lymphomas. Blood.
  • View abstract
  • View PDF
• Müller C, Calkhoven CF, Sha X, Leutz A. (2003) The CCAAT enhancer-binding protein alpha (C/EBPalpha) requires a SWI/SNF complex for proliferation arrest. The journal of biological chemistry.
  • View abstract
  • View PDF
• Calkhoven CF, Muller C, Martin R, Krosl G, Pietsch H, Hoang T, Leutz A. (2003) Translational control of SCL-isoform expression in hematopoietic lineage choice. Genes & Development.
  • View abstract
  • View PDF
• Calkhoven CF, Müller C, Leutz A. (2002) Translational control of gene expression and disease. Trends in molecular medicine.
  • View abstract
  • View PDF
• Calkhoven CF, Müller C, Leutz A. (2000) Translational control of C/EBPalpha and C/EBPbeta isoform expression. Genes & Development.
  • View abstract
  • View PDF
• Calkhoven CF, Snippe L, Ab G. (1997) Differential stimulation by CCAAT/enhancer-binding protein alpha isoforms of the estrogen-activated promoter of the very-low-density apolipoprotein II gene. European journal of biochemistry.
  • View abstract
  • View PDF
• Calkhoven CF, Gringhuis SI, Ab G. (1999) The chicken CCAAT/enhancer binding protein alpha gene. Cloning, characterisation and tissue distribution. Gene.
  • View abstract
  • View PDF
• Calkhoven CF, Ab G. (1996) Multiple steps in the regulation of transcription-factor level and activity. The biochemical journal.
  • View abstract
  • View PDF
• Calkhoven CF, Bouwman PR, Snippe L, Ab G. (1994) Translation start site multiplicity of the CCAAT/enhancer binding protein alpha mRNA is dictated by a small 5' open reading frame. Nucleic Acids Research.
  • View abstract
  • View PDF
• Calkhoven CF, Ab G, Wijnholds J. (1992) c/CEPB, a chicken transcription factor of the leucine-zipper C/EBP family [corrected].. Nucleic Acids Research.
  • View abstract
  • View PDF