My research focuses on cellular mechanisms of aggregation of aberrant and damaged proteins. Abnormal polypeptides that escape proteasome-dependent degradation tend to aggregate and can be transported via microtubules to an aggresome, an organelle where aggregated proteins are degraded by autophagy. Protein aggregation plays a major role in various neurodegenerative disorders. We used synphilin 1, a protein implicated in Parkinson disease, as a model to study these processes in cell cultures. We have demonstrated that contrary to popular believes protein aggregation in a cell is not a spontaneous event and relies upon various cellular elements. We found that the cell senses the levels of defective ribosomal products to activate various stress responses including protein aggregation. Furthermore, we demonstrated that mild slowdown of a ribosome can significantly improve the quality of the newly synthesized polypeptides. We found that Bag3-Hsp70 module implicated in carcinogenesis is involved in sensing of the defective ribosomal products and triggering of the stress responses. We work to identify additional elements of this response.
- St. Petersburg State Chemical-Pharmaceutical Academy, PhD
- St. Petersburg State Polytechnic University, MS
- Published on 7/9/2018
Meriin AB, Narayanan A, Meng L, Alexandrov I, Varelas X, Cissé II, Sherman MY. Hsp70-Bag3 complex is a hub for proteotoxicity-induced signaling that controls protein aggregation. Proc Natl Acad Sci U S A. 2018 Jul 09. PMID: 29987014.
- Published on 8/24/2015
Zaarur N, Xu X, Lestienne P, Meriin AB, McComb M, Costello CE, Newnam GP, Ganti R, Romanova NV, Shanmugasundaram M, Silva ST, Bandeiras TM, Matias PM, Lobachev KS, Lednev IK, Chernoff YO, Sherman MY. RuvbL1 and RuvbL2 enhance aggresome formation and disaggregate amyloid fibrils. EMBO J. 2015 Sep 14; 34(18):2363-82. PMID: 26303906.
- Published on 1/27/2014
Zaarur N, Meriin AB, Bejarano E, Xu X, Gabai VL, Cuervo AM, Sherman MY. Proteasome failure promotes positioning of lysosomes around the aggresome via local block of microtubule-dependent transport. Mol Cell Biol. 2014 Apr; 34(7):1336-48. PMID: 24469403.
- Published on 8/17/2012
Meriin AB, Mense M, Colbert JD, Liang F, Bihler H, Zaarur N, Rock KL, Sherman MY. A novel approach to recovery of function of mutant proteins by slowing down translation. J Biol Chem. 2012 Oct 5; 287(41):34264-72. PMID: 22902621.
- Published on 5/22/2012
Kim G, Meriin AB, Gabai VL, Christians E, Benjamin I, Wilson A, Wolozin B, Sherman MY. The heat shock transcription factor Hsf1 is downregulated in DNA damage-associated senescence, contributing to the maintenance of senescence phenotype. Aging Cell. 2012 Aug; 11(4):617-27. PMID: 22510478.
- Published on 2/22/2012
Meriin AB, Zaarur N, Sherman MY. Association of translation factor eEF1A with defective ribosomal products generates a signal for aggresome formation. J Cell Sci. 2012 Jun 1; 125(Pt 11):2665-74. PMID: 22357952.
- Published on 9/1/2010
Meriin AB, Wang Y, Sherman MY. Isolation of aggresomes and other large aggregates. Curr Protoc Cell Biol. 2010 Sep; Chapter 3:Unit 3.38.1-9. PMID: 20853343.
- Published on 10/1/2009
Ilyinskii PO, Schmidt T, Lukashev D, Meriin AB, Thoidis G, Frishman D, Shneider AM. Importance of mRNA secondary structural elements for the expression of influenza virus genes. OMICS. 2009 Oct; 13(5):421-30. PMID: 19594376.
- Published on 10/14/2008
Wang Y, Meriin AB, Zaarur N, Romanova NV, Chernoff YO, Costello CE, Sherman MY. Abnormal proteins can form aggresome in yeast: aggresome-targeting signals and components of the machinery. FASEB J. 2009 Feb; 23(2):451-63. PMID: 18854435.
- Published on 7/17/2008
Zaarur N, Meriin AB, Gabai VL, Sherman MY. Triggering aggresome formation. Dissecting aggresome-targeting and aggregation signals in synphilin 1. J Biol Chem. 2008 Oct 10; 283(41):27575-84. PMID: 18635553.
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