Patient Care Bio
Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor composed of a HIF alpha subunit and a beta/ARNT subunit. While HIF beta subunit is constitutively expressed, HIF alpha subunit is rapidly degraded at normoxia by the ubiquitin-proteasome pathway. Importantly, it has been shown recently that the prolyl hydroxylation of HIF alpha subunit is required for its ubiquitination and subsequent destruction. The a subunit becomes hydroxylated by a family of newly identified prolyl-4-hydroxylases. Three prolyl hydroxylases namely EGLN1, 2, 3 have been identified to date.
My research focus is on elucidating of the biochemical and biological roles of SM20, the orthologue of EGLN-3, with a specific emphasis on deciphering the effect of SM20 on the differentiation and development of skeletal muscle. Towards this end, we have been using pharmalogical inhibitors to repress the activity of the prolyl hydroxylase, siRNAs to knock down SM20 expression level, and transient transfection strategy to overexpress SM20 to reveal a role for SM20 in the differentiation of cultured skeletal myoblasts. Strikingly, our preliminary results suggest that SM20 is involved in myogenesis. Our intriguing finding prompts us to dissect the underlying mechanism(s). It has been well documented that the myogenic differentiation is mainly orchestrated by a family of muscle regulatory factors (MRFs) including MyoD, myogenin, Myf-5, and MRF4. As a first step, work is in progress to explore the impact of SM20 on these master muscle-specific molecules. Further efforts will be made to identify more complicated molecular basis of SM20 on myogenesis by employing a broad variety of approaches such as (but not limited to) cDNA microarray and proteomics methodologies. In addition, we set out to create the SM20 knock-out mice to obtain more complex picture of how SM20 regulates myogenesis and development. Our study will improve the understanding of the biochemical and biological relevance of SM20 and provide novel insights into the regulation of myogenic differentiation.