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  • Collaborators
    • Dr Ed Laufer, (Department of Genetics and Development, Columbia University Medical Centre, USA)
    • Professor Peter O'Shaughnessy, (Institute of Comparative Medicine, University of Glasgow Veterinary School, Glasgow)
 

Peter J. King PhD
Senior Lecturer in Endocrinology
Centre for Endocrinology

Contact Details:

p.j.king@qmul.ac.uk

Peter King graduated from Cambridge University in 1984 with a degree in Biochemistry. He was awarded a PhD by the Imperial Cancer Research Fund (now CRUK) on transcriptional regulation of the human beta interferon gene and joined the Molecular Endocrinology Department in 1997, being appointed to a lectureship in 2001.

 

Current research interests

Transcriptional regulation of genes in the adrenal cortex, particularly the ACTH receptor MC2-R. Many steroidogenic enzymes are regulated by the transcription factor SF-1 for which there are binding sites in the murine MC2-R promoter around the transcriptional start site. Mutating these sites does not impair the activity of the promoter in adrenal cells indicating the involvement of other trans acting factors   
 
MC2-R transcriptional regulation during adipocyte differentiation. MC2-R is expressed in rodent adipocytes where it responds to ACTH treatment leading to lipolysis. We have shown that it is rapidly upregulated during adipocyte differentiation and the trans acting factor responsible is PPARg2. We have also shown that this promoter activation is transient, whereas MC2-R mRNA expression remains elevated. This is a consequence of a switch in promoter usage from the upstream ‘conventional’ promoter to a downstream novel promoter in the first intron which is driven by a C/EBP site. The mechanism for this switch is being investigated.
MC2-R signalling. The intracellular signalling pathways activated by ACTH through the MC2-R are being investigated with Professor Clark.   

Control of adrenal cortex differentiation and development. The adrenal cortex contains different zones with different steroidogenic function, the zonae glomerulosa, fasciculata and reticularis. We performed a microarray analysis on rat adrenals to identify genes that were differentially expressed in the zona glomerulosa in an attempt to identify potential differentiation regulators. One member of the BMP family is exclusively expressed in the zona glomerulosa and experiments are underway to identify its role in zonation. The promoters of other glomerulosa-specific genes will be analysed in an attempt to identify common transcriptional control mechanisms.

 

Key publications

 

  • Bogdarina, I., Welham, S., King, P.J., Burns, S.P. and Clark, A,J.; (2007). Epigenetic Modification Of The Renin-Angiotensin System In The Fetal Programming Of Hypertension. Circ. Res., 100: 520-526
  • Noon, L.A., Clark, A.J.L, O'Shaughnessy, P. J. and King, P.J.; (2006) A C/EBP Site At ?87 Is Required For The Activation Of A Novel Murine Melanocortin 2-Receptor (MC2-R) Promoter At Late Stages During Adipogenesis. Endocrinol., 147: 6019-6026.
  • Noon, L.A., Bakmanidis, A, Clark, A.J.L, O'Shaughnessy, P. J. and King, P.J.; (2006) Identification of a Novel MC2-R Splice Variant in Murine Adipocytes: Implications For Post-Transcriptional Control of Expression During Adipogenesis. J. Mol. Endocrinol., 37: 415-420.
  • Noon, L.A., Clark, A.J.L. and King, P.J.; (2004); A Peroxisome Proliferator-Response Element In the Murine MC2-R Promoter Regulates Its Transcriptional Activation During Differentiation of 3T3-L1 Adipocytes; J. Biol. Chem.; 279; 22803-22808.
  • Swords, FM, Noon, LA, King, PJ and Clark AJL (2004) Constitutive Activation Of The Human ACTH Receptor Resulting From A Synergistic Interaction Between Two Naturally Occurring Missense Mutations In The MC2R Gene. Mol Cell Endocrinol 213: 149-54
  • Fowkes, RC, Desclozeaux, M, Patel, MV, Aylwin, SJ, King, P, Ingraham, HA and Burrin, JM (2003) Steroidogenic Factor-1 (SF-1) And The Gonadotrope-Specific Element (GSE) Enhance Basal And Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Stimulated Transcription Of The Human Glycoprotein Hormone a-Subunit Gene (a-GSU) In Gonadotropes. Mol Endocrinol, 17: 2177-2188

  • Swords, FM, Baig, A, Malchoff, DM, Malchoff, CD, Thorner, MO, King, PJ, Hunyady, L and Clark, AJL (2002) Impaired Desensitization Of A Mutant Adrenocorticotropin Receptor Associated With Apparent Constitutive Activity. Mol Endocrinol, 16: 2746-53

  • Baig, AH, Swords, FM, Noon, LA, King, PJ, Hunyady, L and Clark, AJL (2001) Desensitization Of The Y1 Cell Adrenocorticotropin Receptor: Evidence For A Restricted Heterologous Mechanism Implying A Role For Receptor-Effector Complexes. J Biol Chem, 276, 44792-44797

 

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Dr. Peter King
 


Research Staff:

  • Dr D. Cavlan
  • Dr C. Sze
  • Dr L. Guasti

PhD Students:

  • K. Cogger

 

 

 

 

 

 
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