CUL4A exhibits tumor-suppressing role via regulation of HUWE1-mediated SMAD3 intracellular shuttling

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F25%3A00639505" target="_blank" >RIV/86652036:_____/25:00639505 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/25:00639505 RIV/00216208:11310/25:10498930

Result on the web

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0304383525002290?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0304383525002290?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.canlet.2025.217663" target="_blank" >10.1016/j.canlet.2025.217663</a>

Result language

angličtina

Original language name

CUL4A exhibits tumor-suppressing role via regulation of HUWE1-mediated SMAD3 intracellular shuttling

Original language description

Changes in cellular physiology and proteomic homeostasis accompanied the initiation and progression of colorectal cancer. Thus, ubiquitination represents a central regulatory mechanism in proteome dynamics. However, the complexity of the ubiquitinating network involved in carcinogenesis remains unclear. This study revealed the tumor-suppressive role of the ubiquitin ligase Cullin4A (CUL4A) in the intestine. We showed that simultaneous loss of CUL4A and hyperactivation of the Wnt pathway promotes tumor development in the distal colon. This tumor development is caused by an accumulation of the inactive SMAD3, a TGF-(3 pathway mediator. Depletion of CUL4A resulted in stabilization of HUWE1, which attenuated SMAD3 function. We showed a correlation between the intracellular localization of CUL4A and colorectal cancer progression, where nuclear CUL4A localization correlates with advanced colorectal cancer progression. In summary, we identified CUL4A as an important regulator of SMAD3 signal transduction competence in a HUWE1-dependent manner and demonstrated a critical role for the crosstalk between ubiquitination and the Wnt/TGF-(3 signaling pathways in gastrointestinal homeostasis.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cancer letters

ISSN

0304-3835

e-ISSN

1872-7980

Volume of the periodical

621

Issue of the periodical within the volume

Jul

Country of publishing house

IE - IRELAND

Number of pages

10

Pages from-to

217663

UT code for WoS article

001469936700001

EID of the result in the Scopus database

2-s2.0-105002010633