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Cullin family proteins and tumorigenesis: genetic association and molecular mechanisms.

Chen Z, Sui J, Zhang F, Zhang C - J Cancer (2015)

Bottom Line: Cullin family proteins function as scaffolds to form numerous E3 ubiquitin ligases with RING proteins, adaptor proteins and substrate recognition receptors.Clinically, cullin-associated E3 ligases have been identified to involve numerous human diseases, especially with regard to multiple cancer types.Over the past few years, our understanding of cullin proteins and their functions in genome stability and tumorigenesis has expanded enormously.

View Article: PubMed Central - PubMed

Affiliation: 1. Orthopedics Department, Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China, 200433.

ABSTRACT
Cullin family proteins function as scaffolds to form numerous E3 ubiquitin ligases with RING proteins, adaptor proteins and substrate recognition receptors. These E3 ligases further recognize numerous substrates to participate in a variety of cellular processes, such as DNA damage and repair, cell death and cell cycle progression. Clinically, cullin-associated E3 ligases have been identified to involve numerous human diseases, especially with regard to multiple cancer types. Over the past few years, our understanding of cullin proteins and their functions in genome stability and tumorigenesis has expanded enormously. Herein, this review briefly provides current perspectives on cullin protein functions, and mainly summarizes and discusses molecular mechanisms of cullin proteins in tumorigenesis.

No MeSH data available.


Related in: MedlinePlus

Cullin proteins affect multiple pathways involved in cancer. Cullin proteins play critical roles in cancer through a variety of mechanisms, including DNA replication and repair, cell cycle control, apoptosis, oxidative stresses, chromatin remodeling, hypoxia, regulation of oncogenes, and signal transduction involved in p53 and WNT. Proteins participate in these processes are also indicated.
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Figure 3: Cullin proteins affect multiple pathways involved in cancer. Cullin proteins play critical roles in cancer through a variety of mechanisms, including DNA replication and repair, cell cycle control, apoptosis, oxidative stresses, chromatin remodeling, hypoxia, regulation of oncogenes, and signal transduction involved in p53 and WNT. Proteins participate in these processes are also indicated.

Mentions: Collectively, cullin proteins play critical roles in cancer through a variety of mechanisms, including DNA damage and repair, cell cycle control, apoptosis, oxidative stresses, chromatin remodeling, regulation of oncogenes, signal transduction involved in p53 and WNT (Figure 3). In which, cullins proteins mainly function as scaffolds to form numerous E3 ligases, and these E3 ligases further recognize different substrates to participate in different cellular processes. Complete inactivation of CRLs causes tumor cell growth suppression, indicating that the major role of CRLs in cancer cells is to target and degrade tumor suppressor proteins in order to sustain an unlimited proliferation 5. Thus, this unique feature of cancer cells confers them much more vulnerable to be targeted against CRLs in therapy 5. It is clear that further studies to explore CRL functions and screen substrates of CRLs in different cancer types. To develop potential anti-cancer agents, it is important to focus on the development of CRL inhibitors by targeting cullin neddylation and CRL-mediated ubiquitination in the future.


Cullin family proteins and tumorigenesis: genetic association and molecular mechanisms.

Chen Z, Sui J, Zhang F, Zhang C - J Cancer (2015)

Cullin proteins affect multiple pathways involved in cancer. Cullin proteins play critical roles in cancer through a variety of mechanisms, including DNA replication and repair, cell cycle control, apoptosis, oxidative stresses, chromatin remodeling, hypoxia, regulation of oncogenes, and signal transduction involved in p53 and WNT. Proteins participate in these processes are also indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4317758&req=5

Figure 3: Cullin proteins affect multiple pathways involved in cancer. Cullin proteins play critical roles in cancer through a variety of mechanisms, including DNA replication and repair, cell cycle control, apoptosis, oxidative stresses, chromatin remodeling, hypoxia, regulation of oncogenes, and signal transduction involved in p53 and WNT. Proteins participate in these processes are also indicated.
Mentions: Collectively, cullin proteins play critical roles in cancer through a variety of mechanisms, including DNA damage and repair, cell cycle control, apoptosis, oxidative stresses, chromatin remodeling, regulation of oncogenes, signal transduction involved in p53 and WNT (Figure 3). In which, cullins proteins mainly function as scaffolds to form numerous E3 ligases, and these E3 ligases further recognize different substrates to participate in different cellular processes. Complete inactivation of CRLs causes tumor cell growth suppression, indicating that the major role of CRLs in cancer cells is to target and degrade tumor suppressor proteins in order to sustain an unlimited proliferation 5. Thus, this unique feature of cancer cells confers them much more vulnerable to be targeted against CRLs in therapy 5. It is clear that further studies to explore CRL functions and screen substrates of CRLs in different cancer types. To develop potential anti-cancer agents, it is important to focus on the development of CRL inhibitors by targeting cullin neddylation and CRL-mediated ubiquitination in the future.

Bottom Line: Cullin family proteins function as scaffolds to form numerous E3 ubiquitin ligases with RING proteins, adaptor proteins and substrate recognition receptors.Clinically, cullin-associated E3 ligases have been identified to involve numerous human diseases, especially with regard to multiple cancer types.Over the past few years, our understanding of cullin proteins and their functions in genome stability and tumorigenesis has expanded enormously.

View Article: PubMed Central - PubMed

Affiliation: 1. Orthopedics Department, Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China, 200433.

ABSTRACT
Cullin family proteins function as scaffolds to form numerous E3 ubiquitin ligases with RING proteins, adaptor proteins and substrate recognition receptors. These E3 ligases further recognize numerous substrates to participate in a variety of cellular processes, such as DNA damage and repair, cell death and cell cycle progression. Clinically, cullin-associated E3 ligases have been identified to involve numerous human diseases, especially with regard to multiple cancer types. Over the past few years, our understanding of cullin proteins and their functions in genome stability and tumorigenesis has expanded enormously. Herein, this review briefly provides current perspectives on cullin protein functions, and mainly summarizes and discusses molecular mechanisms of cullin proteins in tumorigenesis.

No MeSH data available.


Related in: MedlinePlus