Is HNF4A a candidate to study zinc finger protein slug?

Protein-Protein Interactions (PPI) play a crucial role in deciphering function besides identifying candidates. While the experimental analysis is often time consuming involving number of experiments like pulldown assays, they are not necessarily limiting the ability to detect novel protein interactors. In this work, we discuss the role and putative interactors of SNAI2, a slug protein which is involved in the development of cancer progression. The protein interactions have been deciphered by domain pair exclusion method which gives confidence to already precluded interaction pairs. Additionally, conservation patterns of the slug protein have also been analysed by estimating site-specific evolutionary rates at structural level. Based upon the computational analysis, we consider HNF4A could be a putative candidate to study zinc finger protein slug. We believe, this candidate study augmented with structural conservation will definitely provide novel insights into the design and discovery of new interactions for zinc finger class of proteins besides providing possible clues for discovery of various cancer types associated with this class of proteins.

[1]  M. Nieto,et al.  Slug, a zinc finger gene previously implicated in the early patterning of the mesoderm and the neural crest, is also involved in chick limb development. , 1997, Development.

[2]  P. A. Pérez-Mancera,et al.  SLUG (SNAI2) overexpression in embryonic development , 2006, Cytogenetic and Genome Research.

[3]  J. Nesland,et al.  Snail, Slug, and Smad‐interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma , 2005, Cancer.

[4]  Mengqian Chen,et al.  Androgen regulation of prostasin gene expression is mediated by sterol‐regulatory element‐binding proteins and SLUG , 2006, The Prostate.

[5]  A. Look,et al.  Slug Antagonizes p53-Mediated Apoptosis of Hematopoietic Progenitors by Repressing puma , 2005, Cell.

[6]  Christopher J. Lee,et al.  Inferring protein domain interactions from databases of interacting proteins , 2005, Genome Biology.

[7]  Mark D. Johnson,et al.  SNAI2/Slug promotes growth and invasion in human gliomas , 2010, BMC Cancer.

[8]  P. A. Pérez-Mancera,et al.  The radioresistance biological function of the SCF/kit signaling pathway is mediated by the zinc-finger transcription factor Slug , 2003, Oncogene.

[9]  P. A. Pérez-Mancera,et al.  SLUG in cancer development , 2005, Oncogene.

[10]  Damian Szklarczyk,et al.  The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored , 2010, Nucleic Acids Res..

[11]  A. Look,et al.  SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein. , 1999, Molecular cell.

[12]  Yang Liu,et al.  VisANT 4.0: Integrative network platform to connect genes, drugs, diseases and therapies , 2013, Nucleic Acids Res..

[13]  Jeremy J. W. Chen,et al.  Transcription Repressor Slug Promotes Carcinoma Invasion and Predicts Outcome of Patients with Lung Adenocarcinoma , 2005, Clinical Cancer Research.

[14]  Itay Mayrose,et al.  ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures , 2005, Nucleic Acids Res..

[15]  Kazutaka Katoh,et al.  Multiple alignment of DNA sequences with MAFFT. , 2009, Methods in molecular biology.

[16]  Slug expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients , 2006, British Journal of Cancer.

[17]  S. Bapat,et al.  Snail and Slug are major determinants of ovarian cancer invasiveness at the transcription level. , 2005, Gynecologic oncology.

[18]  J. Sundberg,et al.  The Slug gene is not essential for mesoderm or neural crest development in mice. , 1998, Developmental biology.

[19]  Y. Ip,et al.  Human Slug Is a Repressor That Localizes to Sites of Active Transcription , 2000, Molecular and Cellular Biology.

[20]  Dmitrij Frishman,et al.  DIMA 3.0: Domain Interaction Map , 2010, Nucleic Acids Res..