Molecular interactions of HDGF

Understanding molecular interactions are crucial for the control of cellular metabolism, life and death. We therefore examined interactions for HDGF, a protein known to be involved in the development and progression of different cancer types by using protein purification methods coupled to high resolution mass spectrometry. Up to now the molecular mechanism how HDGF influences the biology of cancer cells is unknown. In this approach we have collected evidence that HDGF can be part of RNA containing protein complexes. It copurifies with Nucleolin an already known component of RNA-protein complexes and modulator of RNA stability and translation. Controlling of pre-mRNA splicing and maturation as well as mRNA transport are further important functions assumed by RNA-protein complexes containing Nucleolin (Abdelmohsen et al., 2011).
Interestingly, for HDGF as well as Nucleolin the regulation of BCL-2 - an important regulator of apoptotic pathways and protein with known oncogenic potential - had been shown in independent approaches before (Tsang et al., 2008; Otake et al., 2005). We therefore examined whether the interaction between HDGF and Nucleolin can be modulated by the cellular content of BCL-2 mRNA. The amount of Nucleolin copurifying with HDGF indeed was strongly dependent on the content of cellular BCL-2 mRNA suggesting the existence of an HDGF-Nucleolin-BCL-2 mRNA complex.
We therefore propose the existence of HDGF and Nucleolin containing RNA-protein complexes modulating the stability and translation efficiency of certain mRNAs like BCL-2, thereby presenting a possible molecular mechanism how HDGF contributes to the development and progression of cancer.