Regulation of apoptosis and cell cycle progression by MCL1; Differential role of proliferating cell nuclear antigen

Kenichi Fujise, Di Zhang, Juinn Lin Liu, Edward T H Yeh

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

MCL1 (ML1 myeloid cell leukemia 1), a Bcl-2 (B- cell lyphoma-leukemia 2) homologue, is known to function as an anti-apoptotic protein. Here we show in vitro and in vivo that MCL1 interacts with the cell cycle regulator, proliferating cell nuclear antigen (PCNA). This finding prompted us to investigate whether MCL1, in addition to its anti-apoptotic function, has an effect on cell cycle progression. A bromodeoxyuridine uptake assay showed that the overexpression of MCL1 significantly inhibited the cell cycle progression through the S-phase. The S-phase of the cell cycle is also known to be regulated by PCNA. A mutant of MCL1 that lacks PCNA binding (MCL1Δ4A) could not inhibit cell cycle progression as effectively as wild type MCL1. In contrast, MCL1Δ4A retained its anti-apoptotic function in HeLa cells when challenged by Etoposide. In addition, the intracellular localization of MCL1Δ4A was identical to that of wild type MCL1. An in vitro pull-down assay suggested that MCL1 is the only Bc1-2 family protein to interact with PCNA. In fact, MCL1, not other Bc1-2 family proteins, contained the PCNA-binding motif described previously. Taken together, MCL1 is a regulator of both apoptosis and cell cycle progression, and the cell cycle regulatory function of MCL1 is mediated through its interaction with PCNA.

Original languageEnglish (US)
Pages (from-to)39458-39465
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number50
DOIs
StatePublished - Dec 15 2000
Externally publishedYes

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Myeloid Leukemia
Proliferating Cell Nuclear Antigen
Myeloid Cells
Cell Cycle
Cells
Apoptosis
Assays
S Phase
Apoptosis Regulatory Proteins
Etoposide
Bromodeoxyuridine
B-Cell Leukemia
Proteins
HeLa Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of apoptosis and cell cycle progression by MCL1; Differential role of proliferating cell nuclear antigen. / Fujise, Kenichi; Zhang, Di; Liu, Juinn Lin; Yeh, Edward T H.

In: Journal of Biological Chemistry, Vol. 275, No. 50, 15.12.2000, p. 39458-39465.

Research output: Contribution to journalArticle

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