Role and Regulation of the E3 Ubiquitin Ligase Chip in Glioma
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Role and Regulation of the E3 Ubiquitin Ligase Chip in Glioma
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| Creator |
Paul, Indranil
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| Subject |
Cell Biology & Physiology
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| Description |
Cells use incredibly diverse mechanisms to regulate protein stability and degradation, which
in turn is dependent on the proper functioning of two multi-subunit molecular machineries.
The molecular chaperones help nascent polypeptides fold correctly while 26S proteasome degrades
faulty polypeptides and proteins in response to specific signals. This balance between
folding and degradation is highly regulated and is essential to maintaining normal physiology
and development. Multiple genetic and epigenetic alterations in tumour cells upsets this
balance. Many of the chaperone clients are oncogenes and cancer cells use the chaperone machinery
to protect an array of mutated and over-expressed oncoproteins from misfolding and
degradation. Therefore, the chaperones particularly HSP90 is recognized as a crucial facilitator
of “oncogene addiction” and cancer cell survival. Similarly, and surprisingly, cancer cells
are also extremely sensitive to inhibition of the 26S proteasome. It is now well established
that both chaperones and proteasomes are crucial for survival and propagation of tumour
cells.
Carboxy-terminus of Hsc70 interacting protein or CHIP is a chaperone associated E3 ligase
that ubiquitinates its substrates thus channeling them towards proteasomal degradation.
CHIP is thought to be the central player of the cellular protein quality control system and
several of its reported targets are known to play critical roles in multiple aspects of normal
cell function. Given the number of key nodal oncoproteins that are chaperone clients, manipulation
of the protein CHIP may serve the purpose of collapsing, or significantly weakening, a
cancer cell’s safety net. Therefore in an effort to understand how CHIP relates to the process
of tumourigenesis this thesis asks two broad questions. First, what are the protein targets of
CHIP (i.e., the role) and second, whether and how the intracellular distribution of CHIP is
maintained (i.e., the regulation). Our objective in this work is to understand these aspects of
CHIP in order to gain insights into its personality. In addition to providing important functional
understanding of this critical biological molecule, these insights will help in devising
novel strategies for cancer treatment.
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| Date |
2013
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| Type |
Thesis
NonPeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1845/1/Indranil_Thesis.pdf
Paul, Indranil (2013) Role and Regulation of the E3 Ubiquitin Ligase Chip in Glioma. PhD thesis, Calcutta University. |
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| Relation |
http://www.eprints.iicb.res.in/1845/
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