ePrints@IIScePrints@IISc Home | About | Browse | Latest Additions | Advanced Search | Contact | Help

Chaperone-like protein HYPK and its interacting partners augment autophagy

Choudhury, Kamalika Roy and Bucha, Sudha and Baksi, Shounak and Mukhopadhyay, Debashis and Bhatracharyya, Nitai P (2016) Chaperone-like protein HYPK and its interacting partners augment autophagy. In: EUROPEAN JOURNAL OF CELL BIOLOGY, 95 (6-7). pp. 182-194.

[img] PDF
Eur_Jou_Cel_Bio_95-6_182_2016.pdf - Published Version
Restricted to Registered users only

Download (3MB) | Request a copy
Official URL: http://dx.doi.org/10.1016/j.ejcb.2016.03.003

Abstract

To decipher the function(s) of HYPK, a huntingtin (HTT)-interacting protein with chaperone-like activity, we had previously identified 36 novel interacting partners of HYPK. Another 13 proteins were known earlier to be associated with HYPK. On the basis of analysis of the interacting partners of HYPK, it has been shown that HYPK may participate in diverse cellular functions relevant to Huntington's disease. In the present study, we identified additional 5 proteins by co-immunoprecipitation and co-localization. As of now we have 54 primary interactors of HYPK. From the database we collected 1026 unique proteins (secondary interactors) interacting with these 54 primary HYPK interacting partners. We observed that 10 primary and 91 secondary interacting proteins of HYPK are associated with two types of autophagy processes. We next tested the hypothesis that the hub, HYPK, might itself be involved in autophagy. Using mouse striatal STHdh(Q7)/Hdh(Q7) cell lines, we observed that over expression of HYPK significantly increased background cellular autophagy, while knock down of endogenous HYPK decreased the autophagy level as detected by altered LC3I conversion, BECN1 expression, cleavage of GFP from LC3-GFP, ATG5-ATG12 conjugate formation and expression of transcription factors like Tfeb, Srebp2 and Zkscan3. This result shows that HYPK, possibly with its interacting partners, induces autophagy. We further observed that N-terminal mutant HTT reduced the cellular levels of LC3II and BECN1, which could be recovered significantly upon over expression of HYPK in these cells. This result further confirms that HYPIC could also be involved in clearing mutant HIT aggregates by augmenting autophagy pathway. (C) 2016 Published by Elsevier GmbH.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the ELSEVIER GMBH, URBAN & FISCHER VERLAG, OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
Keywords: HYPK; Autophagy; Cell survival; Huntington's disease; Apoptosis
Department/Centre: Division of Biological Sciences > Centre for Neuroscience
Depositing User: Id for Latest eprints
Date Deposited: 19 Jul 2016 09:55
Last Modified: 19 Jul 2016 09:55
URI: http://eprints.iisc.ac.in/id/eprint/54197

Actions (login required)

View Item View Item