The ends and means of artificially induced targeted protein degradation.
Studies on knockout mutants and conditional mutants are invaluable to biological research and have been used extensively to probe the intricacies of biological systems through loss of function associated with attenuation of a particular protein. Besides, RNAi technology has been developed in recent years to further aid the process of scientific inquiry. Even though, the methods, dealing with DNA and RNA have met with great success, are not without their shortcomings. In order to overcome the inadequacies of existing methods, a host of new techniques, aimed at knockdowns at the protein rather than the nucleic acid level, have been devised. Essentially, these methods can achieve rapid degradation of cellular pools of a target protein in response to an inducible signal coupled with dose-dependent modulation and exquisite temporal control, features which are absent from techniques involving manipulations at the DNA or RNA level. This review aims to provide a broad overview of a gamut of these methods, while highlighting the strengths and weaknesses of each one. Last two decades of advances presented here in the field of targeted protein degradation serve as a beacon to further research and are likely to find applications in the areas of medicine and allied fields of biology.
Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390002, India. chivukula_r@yahoo.com
C Ratna
CR
Prabha
Soumya
S
Mukherjee
Renuka
R
Raman
Swapnali
S
Kulkarni
D005827:Genetics, Microbial / Q000379:methods*; D036341:Intercellular Signaling Peptides and Proteins; D008967:Molecular Biology / Q000379:methods*; D010447:Peptide Hydrolases / Q000235:genetics* / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D059748:Proteolysis; D025801:Ubiquitin / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011506:Proteins; D025801:Ubiquitin; C031017:ornithine decarboxylase antizyme; C049647:snake venom protein C activator; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex