James Franco’s long-awaited Broadway debut in Of Mice and Men is a major draw of the new revival of John Steinbeck’s classic play, which begins performances at the Longacre Theatre on March 19.

But, as director Anna D. Shapiro explains, Steinbeck’s enduring story of friendship and the American dream gone awry is a compelling experience in its own right. “Great plays can be about so many different things — it depends on what time in your life you are encountering them,” says the Chicago-based director, a Tony Award winner for her intensely dramatic production of August: Osage County in 2008.

Steinbeck, who won a Pulitzer Prize for his 1939 novel The Grapes of Wrath and was awarded the Nobel Prize for Literature in 1962, wrote Of Mice and Men first as a novella and subsequently adapted it for the stage. The play, which originally premiered on Broadway in 1937, tells the story of two farm workers, George and Lennie, who drift from job to job in a central California agricultural valley during the Great Depression. George, played by Franco, is tenderly protective of his friend Lennie (Bridesmaids star Chris O’Dowd), a giant of a man who is dependent upon George for protection and guidance. The two friends have plans to one day own a piece of land that they can farm for themselves.

Director Shapiro, whose last production on Broadway was the combustive comedy The Motherf–ker With the Hat, says she is deeply influenced by Steppenwolf, the theater company she has been associated with since 1995. “Everything that I saw in my early life was at that theatre, and I remember vividly their production of Of Mice and Men [a landmark 1980 revival starring Gary Sinise and John Malkovitch]. I am sure that had a huge impact on me.”

Shapiro says she was originally slated to direct the play four years ago, but the plans fell through. “I mostly do new plays, so I was unbelievably excited that someone would think of me for this play, because I have loved it my whole life. It wasn’t until it fell apart — and that really stung — that I realized how much the play meant to me.” Happily, she was approached once again, by different producers, and this time, by a stroke of luck, she reports, the actor Franco was already attached to the production. “That was such a weird, wonderful coincidence because I had spoken to James about the original project but he wasn’t available that time around.”

Franco, an ardent fan of Steinbeck’s writing since his youth, shares Shapiro’s enthusiasm for Of Mice and Men: “it gives us everything about life in a compact little parable: work, friendship, love, jealousy, violence, death, loneliness, everything is there. It’s the ultimate dramatic bromance,” he says.

“To me, it is a play about the American promise, about making your own way — literally, in this story, getting your own piece of land,” says Shapiro. “It’s about the promise that this country has made to a group of people — I should specify white, straight men — and how that promise can systematically take from them the essence of who they are. I think women process disappointment differently, because we never had really been promised anything. But even today, I’m watching even the really successful men who I know managing their own expectations about themselves, trying to figure out what makes them whole.”

In Of Mice and Men, George and Lennie’s best-laid plans are upset by human weakness as well as by the changing economic conditions of the era. Steinbeck wrote his stark fable, of course, at a time when memories of the Depression were fresh in people’s minds; his original title for the story was “Something That Happened.” However, Shapiro notes, the broader themes of the play remain just as timely today.

“When you are raised in a society that is very much about functionality, and you become highly functional in something, that’s who you are,” she says. “What happens when that thing doesn’t exist anymore? In my adulthood alone, I have watched entire industries be wiped out. People’s identities get very confused and lost. What happens between what people expect themselves to be and who they really are — what the world wants from you and what you are really capable of? I’m always interested in that kind of collision.”