Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P43146 (
tumour suppressor
)
5,935
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sustained cellular signalling originated from the receptors located at the plasma membrane is widely associated with cancer susceptibility. Endosomal sorting and degradation of the cell surface receptors is therefore crucial to preventing chronic downstream signalling and tumorigenesis. Since the
E
ndosomal
S
orting
C
omplexes
R
equired for
T
ransport (ESCRT) controls these processes, ESCRT components were proposed to act as
tumour suppressor
genes. However, the
bona fide
role of ESCRT components in tumorigenesis has not been clearly demonstrated. The ESCRT member
HD-PTP
/
PTPN23
was recently identified as a novel haplo-insufficient
tumour suppressor
in vitro
and
in vivo
, in mice and humans. In this mini-review, we outline the role of the ESCRT components in cancer and summarize the functions of
HD-PTP
/
PTPN23
in tumorigenesis.
...
PMID:Role of ESCRT component HD-PTP/
PTPN23
in cancer. 2862 46
HD-PTP
is a
tumour suppressor
phosphatase that controls endocytosis, down-regulation of mitogenic receptors and cell migration. Central to its role is the specific recruitment of critical endosomal sorting complexes required for transport (ESCRTs). However, the molecular mechanisms that enable
HD-PTP
to regulate ESCRT function are unknown. We have characterised the molecular architecture of the entire ESCRT binding region of
HD-PTP
using small angle X-ray scattering and hydrodynamic analyses. We show that
HD-PTP
adopts an open and extended conformation, optimal for concomitant interactions with multiple ESCRTs, which contrasts with the compact conformation of the related ESCRT regulator Alix. We demonstrate that the
HD-PTP
open conformation is functionally competent for binding cellular protein partners. Our analyses rationalise the functional cooperation of
HD-PTP
with ESCRT-0, ESCRT-I and ESCRT-III and support a model for regulation of ESCRT function by displacement of ESCRT subunits, which is crucial in determining the fate of ubiquitinated cargo.
...
PMID:The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function. 2883 Nov 21
