Nuclear and nucleolar targeting sequences of c-erb-A, c-myc, N-myc, p53, HSP70, and HIV tat proteins

C. V. Dang, W. M F Lee

Research output: Contribution to journalArticle

Abstract

Protein import into the cell nucleus requires specific binding of nuclear proteins to the nuclear pore complex. Based on amino acid sequence 'motifs' of known nuclear targeting signals, we identified peptides within a number of nuclear proteins with likely nuclear targeting potential and tested their function by transfecting into cells fusion genes that produce the cytoplasmic 'reporter' protein, pyruvate kinase (PK), joined to the test sequence. Sequences within c-myb (PLLKKIKQ), N-myc (PPQKKIKS), p53 (PQPKKKP), and c-erb-A (SKRVAKRKL) oncoproteins that direct PK hybrids into the nucleus were identified. A peptide (GRKKRRQRRRAP) of the human immunodeficiency virus (HIV) tat protein (Tat), which contains two short basic regions, targets fusion proteins to the nucleolus. The COOH-terminal basic Tat region (QRRRAP) does not target PK hybrid proteins into the nucleus, but mutation of two basic amino acids in this region decreases but does not abolish nucleolar accumulation mediated by the entire Tat nucleolar targeting sequence. Moreover, the c-Myc nuclear targeting sequence fused to the COOH-terminal basic Tat region (PAAKRVKLDQRRRAP) effectively localizes PK hybrids to the nucleus and nucleolus. A similar sequence (FKRKHKKDISQNKRAVRR) in the human heat-shock protein HSP70 also localizes PK to the nucleus and nucleolus.

Original languageEnglish (US)
Pages (from-to)18019-18023
Number of pages5
JournalJournal of Biological Chemistry
Volume264
Issue number30
StatePublished - 1989

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tat Gene Products
Human Immunodeficiency Virus Proteins
Pyruvate Kinase
Viruses
Nuclear Proteins
Proteins
Fusion reactions
Nuclear Pore
Basic Amino Acids
Peptides
Amino Acid Motifs
HSP70 Heat-Shock Proteins
Cell Fusion
Oncogene Proteins
Protein Sorting Signals
Cell Nucleus
Protein Kinases
Amino Acid Sequence
Carrier Proteins
Genes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Nuclear and nucleolar targeting sequences of c-erb-A, c-myc, N-myc, p53, HSP70, and HIV tat proteins. / Dang, C. V.; Lee, W. M F.

In: Journal of Biological Chemistry, Vol. 264, No. 30, 1989, p. 18019-18023.

Research output: Contribution to journalArticle

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