Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignant tumor of the digestive system, characterized by rapid progression and being prone to metastasis. Few effective treatment options are available for PDAC, and its 5-year survival rate is less than 9%. Many cell biological and signaling events are involved in the development of PDAC, among which protein post-translational modifications (PTMs), such as ubiquitination, play crucial roles. Catalyzed mostly by a three-enzyme cascade, ubiquitination induces changes in protein activity mainly by altering their stability in PDAC. Due to their role in substrate recognition, E3 ubiquitin ligases (E3s) dictate the outcome of the modification. Ubiquitination can be reversed by deubiquitylases (DUBs), which, in return, modified proteins to their native form. Dysregulation of E3s or DUBs that disrupt protein homeostasis is involved in PDAC. Moreover, the ubiquitination system has been exploited to develop therapeutic strategies, such as proteolysis-targeting chimeras (PROTACs). In this review, we summarize recent progress in our understanding of the role of ubiquitination in the development of PDAC and offer perspectives in the design of new therapies against this highly challenging disease.
机构:
Stanford Univ, Div Gastroenterol & Hepatol, Sch Med, Stanford, CA 94305 USAStanford Univ, Div Gastroenterol & Hepatol, Sch Med, Stanford, CA 94305 USA
Habtezion, Aida
Edderkaoui, Mouad
论文数: 0引用数: 0
h-index: 0
机构:
Vet Affairs Greater Los Angeles Healthcare Syst, Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA USA
Vet Affairs Greater Los Angeles Healthcare Syst, Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA USA
Univ Calif Los Angeles, Los Angeles, CA USAStanford Univ, Div Gastroenterol & Hepatol, Sch Med, Stanford, CA 94305 USA
Edderkaoui, Mouad
Pandol, Stephen J.
论文数: 0引用数: 0
h-index: 0
机构:
Vet Affairs Greater Los Angeles Healthcare Syst, Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA USA
Vet Affairs Greater Los Angeles Healthcare Syst, Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA USA
Univ Calif Los Angeles, Los Angeles, CA USAStanford Univ, Div Gastroenterol & Hepatol, Sch Med, Stanford, CA 94305 USA
机构:
Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USAUniv Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA
Carpenter, Eileen
Nelson, Sarah
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Surg, 1500 East Med Ctr Dr,2210 Taubman Ctr,SPC 5354, Ann Arbor, MI 48109 USAUniv Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA
Nelson, Sarah
Bednar, Filip
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Surg, 1500 East Med Ctr Dr,2210 Taubman Ctr,SPC 5354, Ann Arbor, MI 48109 USAUniv Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA
Bednar, Filip
Cho, Clifford
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Surg, 1500 East Med Ctr Dr,2210 Taubman Ctr,SPC 5354, Ann Arbor, MI 48109 USAUniv Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA
Cho, Clifford
Nathan, Hari
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Surg, 1500 East Med Ctr Dr,2210 Taubman Ctr,SPC 5354, Ann Arbor, MI 48109 USAUniv Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA
Nathan, Hari
Sahai, Vaibhav
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USAUniv Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA
Sahai, Vaibhav
di Magliano, Marina Pasca
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Surg, 1500 East Med Ctr Dr,2210 Taubman Ctr,SPC 5354, Ann Arbor, MI 48109 USAUniv Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA
di Magliano, Marina Pasca
Frankel, Timothy L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Surg, 1500 East Med Ctr Dr,2210 Taubman Ctr,SPC 5354, Ann Arbor, MI 48109 USAUniv Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA
机构:
VA Greater Los Angeles Hlth Care Syst, Pancreat Res Grp, Dept Med, Los Angeles, CA 90073 USAVA Greater Los Angeles Hlth Care Syst, Pancreat Res Grp, Dept Med, Los Angeles, CA 90073 USA
Pandol, Stephen
Edderkaoui, Mouad
论文数: 0引用数: 0
h-index: 0
机构:VA Greater Los Angeles Hlth Care Syst, Pancreat Res Grp, Dept Med, Los Angeles, CA 90073 USA
Edderkaoui, Mouad
Gukovsky, Ilya
论文数: 0引用数: 0
h-index: 0
机构:VA Greater Los Angeles Hlth Care Syst, Pancreat Res Grp, Dept Med, Los Angeles, CA 90073 USA
Gukovsky, Ilya
Lugea, Aurelia
论文数: 0引用数: 0
h-index: 0
机构:VA Greater Los Angeles Hlth Care Syst, Pancreat Res Grp, Dept Med, Los Angeles, CA 90073 USA
Lugea, Aurelia
Gukovskaya, Anna
论文数: 0引用数: 0
h-index: 0
机构:VA Greater Los Angeles Hlth Care Syst, Pancreat Res Grp, Dept Med, Los Angeles, CA 90073 USA