The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Characterization of a Novel Tripartite Nuclear Localization Sequence in the EGFR Family
Open accessAbstract
Aberrant expression of epidermal growth factor receptor (EGFR) is present in many human tumors. Several reports have shown that EGFR is translocated into the nucleus during liver regeneration and in several types of cells and tissues such as placenta and thyroid. Nuclear EGFR is associated with transcription, DNA synthesis, and DNA repair activity and serves as a prognostic marker in breast carcinoma and oropharyngeal squamous cell cancer. However, the nuclear localization sequence (NLS) of EGFR has not been extensively examined. In this study, we have shown that the juxtamembrane region of EGFR harbors a putative NLS with three clusters of basic amino acids (RRRHIVRKRTLRR (amino acids 645-657)) that mediates the nuclear localization of EGFR. We found that this newly characterized tripartite NLS is conserved among the EGFR family members (EGFR, ErbB2, ErbB3, and ErbB4) and is able to move each to the nucleus. Further, this tripartite NLS could also mediate the nuclear localization of other known cytoplasmic proteins such as pyruvate kinase. We have demonstrated that mutating one of the three basic amino acid clusters (R or K --> A) leads to significant impairment of the nuclear localization of EGFR and that of a green fluorescent protein-pyruvate kinase-NLS reporter protein. Our results show that this tripartite NLS is distinct from the traditional mono- and bipartite NLS and reveal a mechanism that could account for the nuclear localization of membrane receptors.
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Cites
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Cited by
Understanding resistance to EGFR inhibitors—impact on future treatment strategies
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Survival of Cancer Cells Is Maintained by EGFR Independent of Its Kinase Activity
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Self-citationThe Juxtamembrane Region of the EGF Receptor Functions as an Activation Domain
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COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport
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Metadata
- Authors
- Hsu, S.-C., & Hung, M.-C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-04
- Volume
- 282
- Issue
- 14
- Pages
- 10432-10440
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2027877482
- Cited by
- 260
- References
- 63
- FWCI
- 8.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
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